Safety and Effectiveness of Mycophenolate Mofetil in Interstitial Lung Diseases: Insights from a Machine Learning Radiographic Model

<b><i>Introduction:</i></b> Treatment of interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) often includes systemic corticosteroids. Use of steroid-sparing agents is amenable to avoid potential side effects. <b><i>Methods:</i></b> Functional indices and high-resolution computed tomography (HRCT) patterns of patients with non-IPF ILDs receiving mycophenolate mofetil (MMF) with a minimum follow-up of 1 year were analyzed. Two independent radiologists and a machine learning software system (Imbio 1.4.2.) evaluated HRCT patterns. <b><i>Results:</i></b> Fifty-five (<i>n</i> = 55) patients were included in the analysis (male: 30 [55%], median age: 65.0 [95% CI: 59.7–70.0], mean forced vital capacity %predicted [FVC %pred.] ± standard deviation [SD]: 69.4 ± 18.3, mean diffusing capacity of lung for carbon monoxide %pred. ± SD: 40.8 ± 14.3, hypersensitivity pneumonitis: 26, connective tissue disease-ILDs [CTD-ILDs]: 22, other ILDs: 7). There was no significant difference in mean FVC %pred. post-6 months (1.59 ± 2.04) and 1 year (−0.39 ± 2.49) of treatment compared to baseline. Radiographic evaluation showed no significant difference between baseline and post-1 year %ground glass opacities (20.0 [95% CI: 14.4–30.0] vs. 20.0 [95% CI: 14.4–25.6]) and %reticulation (5.0 [95% CI: 2.0–15.6] vs. 7.5 [95% CI: 2.0–17.5]). A similar performance between expert radiologists and Imbio software analysis was observed in assessing ground glass opacities (intraclass correlation coefficient [ICC] = 0.73) and reticulation (ICC = 0.88). Fourteen patients (25.5%) reported at least one side effect and 8 patients (14.5%) switched to antifibrotics due to disease progression. <b><i>Conclusion:</i></b> Our data suggest that MMF is a safe and effective steroid-sparing agent leading to disease stabilization in a proportion of patients with non-IPF ILDs. Machine learning software systems may exhibit similar performance to specialist radiologists and represent fruitful diagnostic and prognostic tools.

Diagnosis of idiopathic pulmonary fibrosis

Interstitial lung disease (ILD) is a group of diseases, involving the inflammation and fibrosis of the interstitium of the lung. ILD is classified according to whether or not the cause is known. Known causes of ILDs include inhalation of environmental substances, drugs, infection, and related connective tissue disease. ILD of unknown cause is called idiopathic ILD. The most common form of idiopathic ILD is idiopathic pulmonary fibrosis (IPF). IPF is a chronic progressive fibrosing ILD that results in the decline of lung function with exertional dyspnea, cough, bibasilar inspiratory crackles, and digital clubbing. The incidence of IPF increases with age, and is predominant in men. The most characteristic feature of IPF is a usual interstitial pneumonia (UIP) pattern detected on high-resolution computed tomography (HRCT). The typical HRCT pattern in case of UIP is honeycombing, with or without traction bronchiectasis or bronchiolectasis; this may be superimposed with fine reticulation. The typical distribution of UIP is subpleural, and there is basal predominance with heterogeneity. A definitive diagnosis of IPF in patients with clinically suspected IPF is made when there is presence of a UIP pattern on HRCT. Bronchoalveolar lavage or surgical lung biopsy is not recommended if a UIP pattern is detected on HRCT. However, bronchoalveolar lavage and surgical lung biopsy are required if probable UIP pattern, indeterminate UIP pattern, or an alternative diagnosis pattern are found on HRCT in order to diagnose IPF. A specific combination of HRCT patterns and histopathological patterns requiring multidisciplinary discussion is necessary to rule in IPF or rule it out.

Development and evaluation of a computer-based decision support system for diffuse lung diseases at high-resolution computed tomography

Background High-resolution computed tomography (HRCT) is essential in narrowing the possible differential diagnoses of diffuse and interstitial lung diseases. Purpose To investigate the value of a novel computer-based decision support system (CDSS) for facilitating diagnosis of diffuse lung diseases at HRCT. Material and Methods A CDSS was developed that includes about 100 different illustrations of the most common HRCT signs and patterns and describes the corresponding pathologies in detail. The logical set-up of the software facilitates a structured evaluation. By selecting one or more CT patterns, the program generates a ranked list of the most likely differential diagnoses. Three independent and blinded radiology residents initially evaluated 40 cases with different lung diseases alone; after at least 12 weeks, observers re-evaluated all cases using the CDSS. Results In 40 patients, a total of 113 HRCT patterns were evaluated. The percentage of correctly classified patterns was higher with CDSS (96.8%) compared to assessment without CDSS (90.3%; P < 0.01). Moreover, the percentage of correct diagnosis (81.7% vs. 64.2%) and differential diagnoses (89.2% vs. 38.3%) were superior with CDSS compared to evaluation without CDSS (both P < 0.01). Conclusion Addition of a CDSS using a structured approach providing explanations of typical HRCT patterns and graphical illustrations significantly improved the performance of trainees in characterizing and correctly identifying diffuse lung diseases.

Quantitative High-resolution Computed tomography Analysis of Antisynthetase Syndrome with Interstitial Pneumonia

Background Non-specific interstitial pneumonia (NSIP) combined with organizing pneumonia (OP) pattern has been confirmed in pathology or radiology. This study is to analyze the correlation between high-resolution computed tomography (HRCT) quantitative indexes (QI) and pulmonary function test parameters (PFTs), and compare differences of HRCT patterns in Antisynthetase Syndrome with interstitial pneumonia (ASS-IP).Methods Data of ASS-IP patients admitted to respiratory department of Ping Jin hospital from January 2014 to December 2019 were retrospectively reviewed.Results 21 ASS-IP patients were enrolled in this study and 3 patients were NSIP, 9 patients were OP and 8 patients were NSIP overlap OP (NSIP/OP) pattern. (1) Volume, Weight percentages of the extracted whole lung volume with attenuation values (V%, W %) and mean lung attenuation (MLA) of non-aerated area is 5.69%, 16.43% and -11.76 Hounsfield unit (Hu). Total MLA of attenuation values(MLAtotal) is -678.97 Hu.(2)FVC and MLA of poorly aerated（r=0.58,P=0.048）, FEV1 and MLA（r=0.79,P=0.001）of poorly aerated, FEV1/FVC（r=0.23,P=0.01） and MLA of normally lung aerated, have linear correlation .(3) DLCO (P=0.049), volume of poorly aerated (Vfibrosis%,P =0.03), and weight of hyper inflated (Whyper%,P=0.02) percentages, and MLAtotal (P=0.01) have significant statistic differences between patients with NSIP/OP or OP patterns, but the therapy improvement time(P=0.41) had no difference. Conclusions QI of HRCT has a good correlation with PFTs and partly reference value to pathological classification of ASS-IP. NSIP/OP may be a common pattern in ASS-IP, fibrosis severity of which is more severe than OP.

COVID-19 Associated Interstitial Lung Disease - An Emerging Entity

Background: COVID-19 disease associated pulmonary sequalae has been increasingly reported after recovery from acute infection. Therefore, we aim to explore the charactersitics of interstitial lung disease in patients with COVID-19.Methods: An observational study was conducted in patients with COVID-19 associated ILD from April 2020 till September 2020. Patients ≥18 years of age with COVID-19 who were diagnosed with ILD based on respiratory symptoms and HRCT chest imaging after the recovery phase of COVID-19 infection were recruited. Data was recorded on a structured proforma, and descriptive analysis was performed using Stata version 12.1.Results: A total of 30 patients with COVID-associated ILD were identified. The mean age of patients was 59.14 (SD 12.60) and 27 (90%) were males. Four HRCT patterns of interstitial lung disease were seen; organizing pneumonia in 10 (33.33%), non-specific interstitial pneumonitis in 17 (56.67%), usual interstitial pneumonitis in 12 (40%) and probable usual interstitial pneumonitis in 14 (46.67%). Diffuse involvement was found in 15 (50%) patients, while peripheral predominance in 15 (50%) and other significant findings were seen in 8 (26.67%) patients. All patients were treated with corticosteroids. The case fatality rate was 16.67%. Amongst the survivors, 8 (32%) recovered completely, 9 (36%) improved, while 8 (32%) patients had static or progressive disease.Conclusions: This is the first study from Southeast Asia that identified COVID-associated interstitial lung disease in patients who had no pre-existing lung disease, highlighting the importance of timely recognition and treatment of an entity that might lead to fatal outcome.

Computed tomography patterns predict clinical course of idiopathic pulmonary fibrosis

Background A new clinical guideline for idiopathic pulmonary fibrosis (IPF) uses high-resolution computed tomography (HRCT) patterns for diagnostic purposes. However, it is unknown how they relate to the IPF clinical course. We aimed to investigate whether HRCT patterns could be used to predict lung function changes and survival in patients with IPF. Methods Clinical data were retrospectively reviewed in 337 patients with IPF (all biopsy-proven cases). HRCT patterns were classified according to the 2018 IPF diagnostic criteria. Results The median follow-up was 46.9 months. The mean age was 62.5 years, and 74.2% were men. Among the HRCT patterns, usual interstitial pneumonia (UIP), probable UIP, indeterminate for UIP, and an alternative diagnosis were identified in 163 (48.4%), 110 (32.6%), 33 (9.8%), and 31 (9.2%) patients, respectively. The indeterminate for UIP group showed higher lung function and exercise capacity and better prognosis than the other groups. They also had a lesser decline in lung function than the other groups during follow-up. In the multivariate Cox analysis, which was adjusted by age, smoking status, lung function, exercise capacity, and use of antifibrotic agents, indeterminate for UIP pattern was found to be an independent prognostic factor (hazard ratio 0.559, 95% confidence interval 0.335–0.933, P = 0.026). However, the probable UIP group had similar lung function changes and prognosis when compared the UIP group. Conclusions Our results suggest that indeterminate for UIP pattern on HRCT may predict a more favorable clinical course in patients with IPF, supporting the validity of the new IPF diagnostic guidelines.

Differential Diagnosis in Patients with HRCT Patterns Suspected for COVID-19 Pneumonia and RT-PCR Negative: A Multidisciplinary Approach for an Appropriate Management

Since 11th March 2020, the World Health Organization has declared that coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a pandemic and a global public health emergency. One of the main problems related to the rapid spread of the pandemic was the low sensitivity of the swabs that were used, resulting in high false negative rates, and the inability of HRCT to distinguish COVID-19 pneumonia from other types of pneumonia, resulting in diagnostic delays and increased infections in the hospital units. To deal with this problem, a multidisciplinary team has been created at the Sant'Orsola-Malpighi University Hospital in Bologna, with the aim of integrating the data of each patient framed as a "COVID suspect" and to get to a correct diagnosis. We analysed some exemplary cases of patients with negative swab but highly suggestive clinical and radiological characteristics for COVID-19 that, thanks to this multidisciplinary team, were then framed as other forms of pneumonia and successfully treated.

AB0605 CLINICAL PROFILE AND CHEST HIGH-RESOLUTION COMPUTED TOMOGRAPHY (HRCT) FINDINGS IN PATIENTS WITH CONNECTIVE TISSUE DISEASES AND INTERSTITIAL LUNG DISEASE: EXPERIENCE OF A SINGLE REFERENCE RHEUMATOLOGY CENTER

Background:Interstitial lung disease (ILD) is a common manifestation of connective tissue diseases (CTDs), and is associated with significant morbidity and mortality. Chest high-resolution computed tomography (HRCT) play an important role in the diagnosis of ILD and may provide prognostic information.Objectives:We aimed to characterize the clinical profile and chest HRCT abnormalities and patterns of patients diagnosed with CTDs and ILD.Methods:In this retrospective, observational study we included 80 consecutive patients with CTDs and ILD referred to a tertiary rheumatology center between 2015 and 2019. From hospital charts we collected clinical data, immunologic profile, chest HRCT findings. HRCT patterns were defined according to new international recommendations.Results:Out of 80 patients, 64 (80%) were women, with a mean age of 55 years old. The most common CTD associated with ILD was systemic sclerosis (38.8%), followed by polymyositis (22.5%) and rheumatoid arthritis (18.8%). The majority of patients had dyspnea on exertion (71.3%), bibasilar inspiratory crackles were present in 56.3% patients and 10% had clubbing fingers. Antinuclear antibodies (ANA) were present in 78.8% patients, and the most frequently detected autoantibodies against extractable nuclear antigen were anti-Scl 70 (28.8%), followed by anti-SSA (anti-Ro, 17.5%), anti-Ro52 (11.3%) and anti-Jo (7.5%). Intravenous cyclophosphamide therapy for 6-12 months was used in 35% of patients, while 5% of patients were treated with mycophenolate mofetil.The most frequent HRCT abnormalities were reticular abnormalities and ground glass opacity. Non-specific interstitial pneumonia (NSIP) was identified in 46.3% CTDs patients. A pattern suggestive of usual interstitial pneumonia (UIP) was present in 32.5% patients, mainly in patients with systemic sclerosis. In 21.3% patients the HRCT showed reticulo-nodular pattern, micronodules and other abnormalities, not diagnostic for UIP or NSIP pattern.Conclusion:Nonspecific interstitial pneumonia (NSIP) is the most common HRCT pattern associated with CTDs. Further prospective longitudinal studies are needed in order to determine the clinical and prognostic significance of various HRCT patterns encountered in CTD-associated ILD and for better patient management.References:[1]Ohno Y, Koyama H, Yoshikaua T, Seki S. State-of-the-Art Imaging of the Lung for Connective Tissue Disease (CTD). Curr Rheumatol Rep. 2015;17(12):69.[2]Walsh SLF, Devaraj A, Enghelmeyer JI, Kishi K, Silva RS, Patel N, et al. Role of imaging in progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150)Disclosure of Interests:None declared

HRCT Patterns of Drug-Induced Interstitial Lung Diseases: A Review

Interstitial Lung Diseases (ILDs) represent a heterogeneous group of pathologies, which may be related to different causes. A low percentage of these lung diseases may be secondary to the administration of drugs or substances. Through the PubMed database, an extensive search was performed in the fields of drug toxicity and interstitial lung disease. We have evaluated the different classes of drugs associated with pulmonary toxicity. Several different high resolution computed tomography (HRCT) patterns related to pulmonary drug toxicity have been reported in literature, and the most frequent ILDs patterns reported include Nonspecific Interstitial Pneumonia (NSIP), Usual Interstitial Pneumonia (UIP), Hypersensitivity Pneumonitis (HP), Organizing Pneumonia (OP), Acute Respiratory Distress Syndrome (ARDS), and Diffuse Alveolar Damage (DAD). Finally, from the electronic database of our Institute we have selected and commented on some cases of drug-induced lung diseases related to the administration of common drugs. As the imaging patterns are rarely specific, an accurate evaluation of the clinical history is required and a multidisciplinary approach—involving pneumologists, cardiologists, radiologists, pathologists, and rheumatologists—is recommended.

Morphological Patterns of Sarcoidosis and Clinical Outcome: Retrospective Analysis through a Multidisciplinary Approach

The aim of this work was to verify the correlations between different pulmonary morphological patterns and functional outcomes in sarcoidosis patients, using a validated score for the comparison between the high-resolution computed tomography (HRCT) of patients belonging to different imaging patterns. From the electronic database of the reference center for interstitial lung diseases of our University Hospital, we retrospectively selected 55 patients with a diagnosis of sarcoidosis according to the American Thoracic Society (ATS) criteria; we evaluated the initial HRCT examination and pulmonary function tests collected at baseline and after a year. Patients were divided into typical (48% of patients) and atypical (52%) HRCT patterns, and a computer tomography activity score (CTAS) was associated with each HRCT appearance detected; clinical history, impact of therapy, and extra-thoracic locations were also considered. We found that worsening of diffusing capacity for carbon monoxide (DLCO) is related to the CTAS (r = −0.20, p = 0.01), and there was an inverse correlation between the variation of forced vital capacity (FVC) and the value of the CTAS (r = −0.30, p = 0.23) in the subgroup of patients with atypical patterns. CTAS were higher in patients with extra-pulmonary localizations (p = 0.05) and the subgroup of patients with extra-thoracic locations and atypical manifestations had a greater worsening in terms of variation of FVC (p = 0.03) and DLCO% (p = 0.04). No difference between treated and untreated patients was found.