Definite Usual Interstitial Pneumonia Research Articles

Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial

ObjectivesCertain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). MethodsIn this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase) followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. ResultsTwenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3–99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6–6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). ConclusionsChemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

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.

Nintedanib and pirfenidone for idiopathic pulmonary fibrosis in King Abdulaziz Medical City, Riyadh: Real-life data.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive age-related lung disease causing relentless fibrosis of the lung parenchyma. Currently, pirfenidone and nintedanib are the two antifibrotic drugs, approved for the treatment of IPF. Both are shown to slow progression by preserving lung functions from rapid decline compared to a placebo. We are reporting a real-life patient experience using these two antifibrotic medications (AFMs) in our tertiary care hospital. A retrospective cohort study was conducted for all IPF cases diagnosed in multidisciplinary meetings between 2015 and 2020 at KAMC, Riyadh (Saudi Arabia). We are reporting patients' demographics, lung function, survival, tolerance, side effects, or death in patients taking AFMs. A total of 81 cases were identified. The majority of patients aged 67 years (68%) were men with a median age of 68 years. Late presentation, severe disease, and definite usual interstitial pneumonia patterns were reported in 60% of our patients. The average number of hospital admissions before starting treatment was 1 (range: 0-3) in the nintedanib group and 1.4 (range: 1.2-5) in the pirfenidone group. There was an increase in the number of hospital admissions in the group started on pirfenidone 1.7 (range: 1.9-8) compared to nintedanib 0.5 (range: 0-3), P = 0.001. The observed mortality outcome in this cohort was 4 (11%) and 12 (27%) for nintedanib and pirfenidone, respectively. The predominant side effects were gastrointestinal symptoms for both the groups 18 (22%). Pirfenidone and nintedanib are the available approved antifibrotic agents used for many years to treat IPF patients. Real-life data showed better tolerability than reported in the West, good compliance, and a manageable side effect profile in this group of elderly and severe IPF patients.

WITHDRAWN

SESSION TITLE: Systemic Diseases Causing Pulmonary Havoc SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is an immune-mediated disease characterized by necrotizing vasculitis of the small blood vessels. Pulmonary involvement is common in AAV. Nodules and pleural effusions are the most common pulmonary finding in AAV. Fibrosing interstitial lung disease (ILD) is rarely associated with AAV, and it has a significant prognostication impact. We present a case of usual interstitial pneumonia (UIP) found in a patient with anti-Myloperoxidase (MPO) ANCA and rapidly progressive disease. CASE PRESENTATION: A 71-year-old female presented to the hospital with progressive exertional dyspnea and weakness for several months. Her physical exam was remarkable for bilateral basilar crackles. Oxygen saturation was 91% on ambient air. Chest radiograph showed lower zones interstitial infiltrates. Computed tomography of the chest showed diffuse reticular opacities in both lungs with honeycombing and traction bronchiectasis consistent with definite usual interstitial pneumonia (UIP) pattern. Laboratory evaluation revealed elevated serum creatinine (5.73 mg/dL). Immunology tests showed elevated anti-MPO ANCA titers. A renal biopsy showed the presence of pauci-immune crescentic glomerulonephritis, confirming the diagnosis of ANCA-mediated vasculitis. The patient was treated with plasmapheresis and 500 mg of intravenous methylprednisolone for three days, followed by cyclophosphamide and a medium dose of prednisone. Her kidney function improved, and she was then discharged to follow-up with pulmonary clinic for initiation of anti-fibrotic. DISCUSSION: ANCA-associated vasculitis (AAV) is a small-vessel vasculitis that can involve multiple organs. Pulmonary involvement has been reported in 25%–80% of cases. Sometimes, it can be the initial manifestation of the disease. The most common form of pulmonary involvement in AAV is diffuse pulmonary nodules, with or without cavitation and pleural effusions. Occasionally, patients can present with fibrosing-ILD, particularly with anti-MPO. This presentation is more prevalent in males and the elderly. Among AAV patients with ILD, UIP is the most frequent radiographic pattern. Non-specific interstitial pneumonia (NSIP) pattern can also be seen. ILD has been linked to increased mortality in AAV patients, particularly those with a UIP pattern. Treatment of fibrosing-ILD in AAV patients is not well established, with a questionable role for immunosuppression. Anti-fibrotic agents might be helpful in patients with a UIP pattern. CONCLUSIONS: UIP is rarely associated with AAV, and it can be the leading diagnostic manifestation. A careful clinical history and laboratory evaluation should be performed in patients with UIP to identify and treat any underlying systemic disease. UIP is a poor prognostic sign in AAV. Clinical trials are needed to establish the role of anti-fibrotic in treating this condition. Reference #1: Maillet T, Goletto T, Beltramo G, Dupuy H, Jouneau S, Borie R, Crestani B, Cottin V, Blockmans D, Lazaro E, Naccache JM, Pugnet G, Nunes H, de Menthon M, Devilliers H, Bonniaud P, Puéchal X, Mouthon L, Bonnotte B, Guillevin L, Terrier B, Samson M; French Vasculitis Study Group (FVSG). Usual interstitial pneumonia in ANCA-associated vasculitis: A poor prognostic factor. J Autoimmun. 2020 Jan;106:102338. doi: 10.1016/j.jaut.2019.102338. Epub 2019 Sep 27. PMID: 31570253. Reference #2: Mohammad AJ, Mortensen KH, Babar J, Smith R, Jones RB, Nakagomi D, Sivasothy P, Jayne DRW. Pulmonary Involvement in Antineutrophil Cytoplasmic Antibodies (ANCA)-associated Vasculitis: The Influence of ANCA Subtype. J Rheumatol. 2017 Oct;44(10):1458-1467. doi: 10.3899/jrheum.161224. Epub 2017 Aug 1. PMID: 28765242. Reference #3: Zhou P, Ma J, Wang G. Impact of interstitial lung disease on mortality in ANCA-associated vasculitis: A systematic literature review and meta-analysis. Chron Respir Dis. 2021 Jan-Dec;18:1479973121994562. doi: 10.1177/1479973121994562. PMID: 33605150; PMCID: PMC7897823. DISCLOSURES: No relevant relationships by Mais Abdou No relevant relationships by Khaled Alshabani

Reticulation pattern without honeycombing on high-resolution CT is associated with the risk of disease progression in interstitial lung diseases

BackgroundThe disease course of idiopathic pulmonary fibrosis (IPF) is progressive and occasionally, other types of interstitial lung disease (ILD) may progress similarly to IPF. This study aimed to evaluate risk factors for disease progression within 24 months in patients with various ILDs.MethodsThis prospective study obtained 97 patients with a suspected ILD who underwent a transbronchial lung cryobiopsy. The extent of several high-resolution computed tomography (HRCT) patterns was assessed. Due to the inclusion criteria the study population presented a low extent of honeycombing and definite usual interstitial pneumonia (UIP) pattern on HRCT suggesting an early stage of ILD. Disease progression within 24 months despite treatment was defined as a relative decline of ≥ 10% in forced vital capacity (FVC), or a relative decline in FVC of ≥ 5% and one of the three additional criteria: (1) a decline in diffusion capacity to carbon monoxide (DLCO) ≥ 15%; (2) increased fibrosis on HRCT; (3) progressive symptoms, or progressive symptoms and increased fibrosis on HRCT. The same definition was utilized in patients with IPF and other ILDs. Risk factors for disease progression were evaluated in a multivariable logistic regression model.ResultsDisease progression was revealed in 52% of the patients with ILD, 51% of the patients with IPF, and 53% of the patients with other types of ILD. A high extent of reticulation on HRCT (Odds ratio [OR] 3.11, 95% Confidence interval [CI] 1.21–7.98, P = 0.019) and never smoking (OR 3.11, CI 1.12–8.63, P = 0.029) were associated with disease progression whereas platelet count (OR 2.06 per 100 units increase, CI 0.96–4.45, P = 0.065) did not quite reach statistical significance.ConclusionHigher extent of reticulation on HRCT and never smoking appeared to associate with the risk of disease progression within 24 months in ILD patients without honeycombing. Approximately half of the patients with ILD revealed disease progression, and similar proportions were observed in patients with IPF and in other types of ILD.

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.

Estimating the Clinical Impact of Photon-Counting-Detector CT in Diagnosing Usual Interstitial Pneumonia.

The aim of this study was to evaluate the clinical impact of a higher spatial resolution, full field-of-view investigational photon-counting detector computed tomography (PCD-CT) on radiologist confidence in imaging findings and diagnosis of usual interstitial pneumonia (UIP) compared with conventional energy-integrating detector CT (EID-CT). Patients suspected of interstitial lung disease were scanned on a PCD-CT system after informed consent and a clinically indicated EID-CT. In 2 sessions, 3 thoracic radiologists blinded to clinical history and scanner type evaluated CT images of the right and left lungs separately on EID- or PCD-CT, reviewing each lung once/session, rating confidence in imaging findings of reticulation, traction bronchiectasis, honeycombing, ground-glass opacities (GGOs), mosaic pattern, and lower lobe predominance (100-point scale: 0-33, likely absent; 34-66, indeterminate; 67-100, likely present). Radiologists also rated confidence for the probability of UIP (0-20, normal; 21-40, inconsistent with UIP; 41-60, indeterminate UIP; 61-81; probable UIP; 81-100, definite UIP) and graded image quality. Because a confidence scale of 50 represented completely equivocal findings, magnitude score (the absolute value of confidence scores from 50) was used for analysis (higher scores were more confident). Image noise was measured for each modality. The magnitude score was compared using linear mixed effects regression. The consistency of findings and diagnosis between 2 scanners were evaluated using McNemar test and weighted κ statistics, respectively. A total of 30 patients (mean age, 68.8 ± 11.0 years; M:F = 18:12) underwent conventional EID-CT (median CTDI vol , 7.88 mGy) and research PCD-CT (median CTDI vol , 6.49 mGy). The magnitude scores in PCD-CT were significantly higher than EID-CT for imaging findings of reticulation (40.7 vs 38.3; P = 0.023), GGO (34.4 vs 31.7; P = 0.019), and mosaic pattern (38.6 vs 35.9; P = 0.013), but not for other imaging findings ( P ≥ 0.130) or confidence in UIP (34.1 vs 22.2; P &lt; 0.059). Magnitude score of probability of UIP in PCD-CT was significantly higher than EID-CT in one reader (26.0 vs 21.5; P = 0.009). Photon-counting detector CT demonstrated a decreased number of indeterminate GGO (17 vs 26), an increased number of unlikely GGO (74 vs 50), and an increased number of likely reticulations (140 vs 130) relative to EID-CT. Interobserver agreements among 3 readers for imaging findings and probability of UIP were similar between PCD-CT and EID-CT (intraclass coefficient: 0.507-0.818 vs 0.601-0.848). Photon-counting detector CT had higher scores in overall image quality (4.84 ± 0.38) than those in EID-CT (4.02 ± 0.40; P &lt; 0.001) despite increased image noise (mean 85.5 vs 36.1 HU). Photon-counting detector CT provided better image quality and improved the reader confidence for presence or absence of imaging findings of reticulation, GGO, and mosaic pattern with idiosyncratic improvement in confidence in UIP presence.

Radiologic-pathologic correlation of interstitial lung abnormalities and predictors for progression and survival.

To evaluate radiologic and histologic correlations for interstitial lung abnormalities (ILAs) and to investigate radiologic or pathologic features contributing to disease progression and mortality. From 268 patients who underwent surgical lung biopsy between January 2004 and April 2019, 45 patients with incidentally detected ILA and normal pulmonary function were retrospectively included. CT features were classified as subpleural fibrotic or non-fibrotic, and changes in ILA over at least 2 years of follow-up were evaluated. Histologic findings were categorized as definite, probable, indeterminate, or alternative diagnosis for usual interstitial pneumonia (UIP) patterns. Overall and progression-free survival were calculated using the Kaplan-Meier method, and the Cox proportional hazard method was used to examine predictors for ILA progression and survival. Among 36 subpleural fibrotic ILA subjects, 25 (69%) showed definite or probable UIP patterns, and 89% (8/9) of subpleural non-fibrotic ILA subjects showed an indeterminate or alternative diagnosis for UIP pattern on histopathology. On the radiologic-pathologic correlation, reticular opacity of fibrotic ILA was correlated with patchy involvement of fibrosis, and ground-glass attenuation of non-fibrotic ILA corresponded to diffuse interstitial thickening. The median progression time of ILA was 54 months, and fibrotic ILA increased the likelihood of progression (hazard ratio, 2.42; p= 0.017). The median survival time of ILA subjects was 123 months, and fibrotic ILA was associated with an increased risk of death (hazard ratio, 9.22; p = 0.025). Subpleural fibrotic ILAs are associated with pathologic UIP patterns, and it is important to recognize subpleural fibrotic ILA on CT to predict disease progression and mortality. • In total, 69% of subpleural fibrotic ILA showed definite or probable UIP patterns, while 11% of subpleural non-fibrotic ILA showed definite or probable UIP patterns. • Subpleural fibrotic ILA was associated with an increased rate of progression (hazard ratio, 2.42; p= 0.017), and the median progression-free time was 40 months. • Subpleural fibrotic ILA had an increased risk of death (hazard ratio, 9.22; p = 0.025), and the median survival time was 86 months.

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.

Radiological and Physiological Predictors of IPF Mortality.

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) has a variable clinical course, which ranges from being asymptomatic to progressive respiratory failure. The purpose of this study was to evaluate the novel clinical parameters of IPF patients who receive an anti-fibrotic agent. Materials and Methods: From January 2011 to January 2021, we identified 39 IPF patients at Okinawa Chubu Hospital. Clinical information was obtained, such as laboratory data, pulmonary function test (PFT) results, and chest images, including of soft tissue thickness and the high-resolution computed tomography (HRCT) pattern at diagnosis. Results: The mean age was 72.9 ± 7.0 (53–85); 27 patients were men and 12 were women. The mean body mass index was 25.1 ± 3.9 (17.3–35). Twenty-four were active smokers and the median number of packs per year was 20. Regarding laboratory findings, mean white blood cell (WBC), lactate dehydrogenase (LDH), and Krebs Von den Lungen-6 (KL-6) values were 7816 ± 1859, 248 ± 47, and 1615 ± 1503, respectively. In PFT, the mean percent predicted FVC, percent predicted total lung capacity, percent predicted functional residual capacity (FRC), and percent predicted diffusion capacity of the lung for carbon monoxide (DLco) were 66.8 ± 14.9%, 71.8 ± 13.7%, 65 ± 39.6%, and 64.6 ± 27.9%, respectively. In chest radiological findings, soft tissue thickness at the right 9th rib was 26.4 ± 8.8 mm. Regarding chest HRCT patterns, 15 showed the definite usual interstitial pneumonia (UIP) pattern, 16 showed the probable UIP pattern, and eight showed the indeterminate for UIP pattern. In the treatment, 24 patients received pirfenidone and 15 patients took nintedanib. The mean observation period was 38.6 ± 30.6 months and 24 patients died. The median survival time was 32.4 months (0.9–142.5). Multivariate analysis adjusted for age showed that both soft tissue thickness [Hazard ratio (HR): 0.912, 95% confidence interval (CI): 0.859–0.979, p-value: 0.009] and percent FRC [HR: 0.980, 95% CI: 0.967–0.992, p-value: 0.002] were robust predictors of IPF mortality. Conclusions: In IPF patients treated with anti-fibrotic agents, both soft tissue thickness at the right 9th rib shown on the chest radiograph and %FRC can be novel predictors of IPF mortality.

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. DISCLOSURES: Employee relationship with Veracyte, Inc Please note: 2 years Added 04/25/2021 by Sangeeta Bhorade, source=Web Response, value=Salary Speaker/Speaker's Bureau relationship with Genentech Please note: 2019-2020 Added 04/30/2021 by Amy Case, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2019-2020 Added 04/30/2021 by Amy Case, source=Web Response, value=Honoraria Advisory Committee Member relationship with Veracyte Please note: 2021 Added 04/30/2021 by Amy Case, source=Web Response, value=Honoraria Advisory Committee Member relationship with Boehringer-Ingelheim Please note: 2021 Added 04/30/2021 by Amy Case, source=Web Response, value=Honoraria No relevant relationships by Sachin Chaudhary, source=Web Response Employee relationship with Veracyte Please note: >$100000 by Jing Huang, source=Web Response, value=Salary Employee relationship with Veracyte Please note: >$100000 by Marla Johnson, source=Web Response, value=Salary Employee relationship with Veracyte, Inc. Please note: 2008-present Added 05/10/2021 by Giulia Kennedy, source=Web Response, value=Salary No relevant relationships by Michael Kreuter, source=Web Response Advisory and speaker bureau relationship with Boehringer Ingelheim Please note: $20001 - $100000 by Joseph Lasky, source=Web Response, value=Fees Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 by Joseph Lasky, source=Web Response, value=Fees Advisory Committee Member relationship with Veracyte Please note: $1-$1000 by Joseph Lasky, source=Web Response, value=Honoraria Consultant relationship with Galecto Please note: 2019-2021 Added 04/30/2021 by Joseph Lasky, source=Web Response, value=Consulting fee Employee relationship with Veracyte Please note: >$100000 by Lori Lofaro, source=Web Response, value=Salary Advisory Committee Member relationship with veracyte Please note: 2020-2021 Added 04/30/2021 by Mary Beth Scholand, source=Web Response, value=Consulting fee Advisory Committee Member relationship with genentech Please note: 2020-2021 Added 04/30/2021 by Mary Beth Scholand, source=Web Response, value=Consulting fee Advisory Committee Member relationship with united therapeutics Please note: 2020-2021 Added 04/30/2021 by Mary Beth Scholand, source=Web Response, value=Consulting fee No relevant relationships by Jennifer Tom, source=Web Response Consultant relationship with Boehringer Ingelheim Please note: 2017-Currently Added 04/30/2021 by Avraham Unterman, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Remedy Cell Please note: 2020-Currently Added 04/30/2021 by Avraham Unterman, source=Web Response, value=Consulting fee

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.

Complete regression of pulmonary squamous carcinoma in IPF following gemcitabine plus cisplatin: a case report and literature review

BackgroundLung cancer is one of the most common co-morbid conditions in patients with idiopathic pulmonary fibrosis (IPF) and negatively affects the prognosis of IPF; Current guidelines for the management of IPF do not give a clear statement on how to manage these patients, and traditional chemotherapy for lung cancer had a limited efficiency rate. Here, we present a rare case of primary lung squamous carcinoma in a patient with IPF whose tumor completely regressed following gemcitabine plus cisplatin therapy; the cancer was no longer detectable after 2 years upon follow-up.Case presentationSixty-seven year-old male patient with IPF was admitted to hospital due to acute onset hemoptysis. In addition to a definite usual interstitial pneumonia (UIP) pattern, a chest CT scan showed a non-enhancing nodular opacity in the right upper lobe and an enhancing nodule in the right lower lobe. Bronchoscopic biopsy of the nodule in the right lower lobe revealed squamous lung cancer. After 2 cycles of chemotherapy with gemcitabine and cisplatin, the tumor in the right lower lobe was no longer detectable after 2 years of follow-up; however, the nodule in the right upper lobe had increased significantly. Finally, Mycobacterium tuberculosis (MTB) was cultured from the bronchoalveolar (BAL) sample submitted at the last evaluation, and the patient was confirmed to have active pulmonary TB.ConclusionWe report the first documented case of complete pulmonary squamous carcinoma regression in IPF following gemcitabine plus cisplatin. Traditional chemotherapy is considered inadequate to cause the resulting regression of the tumor. The concomitant active pulmonary tuberculosis possibly underlies the mechanism.

Predictive factors of mortality in rheumatoid arthritis-associated interstitial lung disease analysed by modified HRCT classification of idiopathic pulmonary fibrosis according to the 2018 ATS/ERS/JRS/ALAT criteria

Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Although usual interstitial pneumonia (UIP) pattern was reported as a poor prognostic factor, in clinical practice, we often cannot classify high-resolution computed tomography (HRCT) patterns specifically as UIP or nonspecific interstitial pneumonia (NSIP). This study of RA-ILD aimed to elucidate prognosis by using our modified HRCT pattern classification according to the latest guideline on idiopathic pulmonary fibrosis (IPF). We analysed the medical records of 96 consecutive patients diagnosed as having RA-ILD. The modified HRCT classifications were defined as definite UIP, probable UIP, indeterminate for UIP (i.e., early UIP or NSIP/UIP), NSIP, organizing pneumonia (OP), NSIP+OP, and unclassifiable. Predictors of prognosis were determined using Cox regression models. Our RA-ILD cohort included definite UIP (21%), probable UIP (20%), indeterminate for UIP (30%) including NSIP/UIP (27%), alternative diagnosis (29%) including NSIP (14%), and other patterns. Interrater agreement for HRCT pattern was good (κ=0.75). Multivariate analysis showed that older age, history of acute exacerbation, and radiological honeycombing were negative prognostic factors of mortality. NSIP/UIP pattern of indeterminate for UIP was the major pattern in RA-ILD. Although classifications of HRCT patterns were not related to survival, the presence of radiological honeycombing could be a useful predictor of poor prognosis, and acute exacerbation of ILD can seriously impact patient survival regardless of the presence of a UIP or indeterminate for UIP pattern. Our modified HRCT classification based on the latest IPF guideline might be useful to assess appropriate strategies of diagnosis in future RA-ILD studies, and radiological honeycombing could better predict poor prognosis rather than HRCT pattern.

Pirfenidone in real life: A retrospective observational multicentre study in Italian patients with idiopathic pulmonary fibrosis.

Real-world data on pirfenidone treatment of patients with idiopathic pulmonary fibrosis (IPF) are limited. This study assessed the effectiveness of pirfenidone in a large real-life Italian IPF cohort. IRENE was an observational, retrospective study of patients with IPF treated with pirfenidone in routine clinical practice (18 centres). At Month 6, a mandatory re-evaluation of forced vital capacity (FVC) decline (absolute change < 10%) was required to continue pirfenidone. The primary effectiveness outcomes were absolute change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12. Safety was described by adverse event (AE) occurrence. Prespecified subgroups included sex, age, presence/absence of emphysema, usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and baseline lung function. The study included 379 patients (mean age, 67.6 years; 78.1% male). Mean change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12 were -81.8 mL (SD, 419.6 mL; P = 0.002) and 16.0% (95% CI, 12.2-20.9%), respectively. Disease progression was similar across prespecified subgroups, including patients with definite vs possible UIP. Overall, 211 AEs occurred in 149 patients (39.3%), with serious AEs in 31 patients (8.2%) and 9 discontinuations due to AEs. Skin and gastrointestinal AEs were most frequent. Fifteen patients (4.0%) died. The decline in FVC and the safety profile observed in this real-world IPF cohort were consistent with the findings of the Phase III pirfenidone trials.

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.