Idiopathic Interstitial Lung Disease Research Articles

Antifibrotická terapie a její indikace u intersticiální plicní fibrózy

Idiopathic pulmonary fibrosis and chronic fibrotic interstitial lung disease with progressive phenotype are characterized by fibrotic lung parenchyma. Current antifibrotic treatment does not affect pre-existing lung parenchyma fibrosis, but prevents fibrosis progression and reduces mortality by reducing fibrotization. This work summarizes fibrotic lung processes and their treatment options.

Pirfenidone mitigates TGF-β1-mediated fibrosis in an idiopathic inflammatory myositis-associated interstitial lung disease model.

Idiopathic inflammatory myositis (IIM) is a group of rare diseases of unknown etiology, with a pathognomonic muscular deficiency. Antisynthetase syndrome is a subtype of IIM with an associated interstitial lung disease (ILD), characterized by pulmonary inflammation and fibrosis mediated by TGF-β. Pirfenidone is a new molecule with anti-inflammatory and anti-fibrotic properties, used for the treatment of idiopathic ILD, but has never been assessed in IIM. The aim of our study is to evaluate the effect of pirfenidone on IIM-associated ILD. Thirty-two BALB/c male mice were divided into three groups: Sham, IIM-untreated (IIM), and IIM pirfenidone-treated (IIM+PIR). IIM was induced by intramuscular injections of guinea pig muscle myosin extract and intraperitoneal injections of Pertussis toxin. Pirfenidone was given orally at a dose of 30mgkg-1day-1 for two months. Muscle force, blood and bronchoalveolar lavage fluid samples, as well as muscle and lung tissues, were analyzed. Progressive deterioration of muscle force and infiltration of the muscular tissue by inflammatory cells were observed with IIM. Auto-immune antibodies specific to the antisynthetase syndrome were also increased in IIM mice. Pirfenidone attenuated IIM-associated ILD with anti-inflammatory properties evidenced by decreased peribronchial inflammation and TGF-β1 in bronchoalveolar lavage fluid. Likewise, pirfenidone attenuated pulmonary fibrosis by fine-tuning TGF-β1-mediated epithelial-to-mesenchymal and fibrotic signaling pathways; pro-fibrotic SMAD3, ZEB2 and STAT1 expression and activation were decreased, whereas anti-fibrotic SMAD2 activation was increased. This study unravels for the first time that pirfenidone has the potential to fine-tune TGF-β1 fibrotic signaling in IIM-associated ILD.

P221 Autoantibodies are common in patients with idiopathic interstitial lung disease, suggesting a high prevalence of undiagnosed autoimmune connective tissue disease

Abstract Background/Aims In some patients, interstitial lung disease (ILD) may be the dominant or even sole manifestation of an otherwise unrecognised autoimmune connective tissue disease (CTD). Accurate diagnosis can be challenging given considerable overlap of the clinical, radiological and histological disease features. Distinguishing CTD related ILD (CTD-ILD) from idiopathic ILD, enables appropriate immunosuppressive treatment, informs prognosis and facilitates monitoring for other CTD associated complications. Occasionally a lung biopsy may be necessary to ensure accurate diagnosis. Autoantibodies are a hallmark feature of CTD, are highly disease specific and their presence is strongly suggestive of covert CTD-ILD. We investigated patients with idiopathic ILD for the presence of autoantibodies that may suggest misdiagnosis. Methods The serum from three subgroups of patients recruited to UK Biomarkers of Interstitial Lung Disease (BILD) were analysed: 171 with a diagnosis of idiopathic ILD and non-specific organising pneumonia on HRCT and 27 with a diagnosis of idiopathic ILD and cryptogenic organising pneumonia on HRCT. Autoantibody status was determined by radio-immunoprecipitation. Results Results are summarised in Table 1. Overall CTD-autoantibodies were identified in 15.6% of patients with idiopathic ILD, and were more common in those with NSIP, see table. Autoantibodies identified included those readily detectable e.g. anti-Jo1, in addition to rarer antibodies not included in standard assays e.g. anti-EIF3. Nearly half of all autoantibodies detected were anti-synthetase autoantibodies. Conclusion Covert-CTD is likely to be common amongst patients diagnosed with idiopathic ILD, particularly idiopathic NSIP. More specific guidance on autoantibody testing could improve diagnosis and ensure patients receive appropriate immunosuppressive treatment. Disclosure S. Tansley: None. C. Cotton: None. F.K. McMorrow: None. H. Lu: None. R.P. New: None. L.G. Spencer: None. N.J. McHugh: None. R.G. Cooper: None.

OA12 Autoantibodies are common in patients labelled as “idiopathic” interstitial lung disease suggesting a high prevalence of undiagnosed autoimmune connective tissue disease

Abstract Background/Aims In some patients, interstitial lung disease (ILD) may be the dominant or even sole clinically overt manifestation of an otherwise unrecognised autoimmune connective tissue disease (CTD). Accurate diagnosis can be challenging given considerable overlap of the clinical, radiological and histological disease features. Distinguishing CTD-related ILD (CTD-ILD) from idiopathic ILD can avoid a lung biopsy, enables appropriate immunosuppressive treatment, informs prognosis and facilitates monitoring for other CTD-associated complications. Autoantibodies are a hallmark feature of CTD, are highly disease-specific and their presence is strongly suggestive of covert CTD-ILD. We investigated patients who had been labelled with “idiopathic” ILD by their local hospital teams for the presence of autoantibodies that may suggest misdiagnosis. Methods Serum from two groups of patients recruited to UK Biomarkers of Interstitial Lung Disease (BILD) were analysed: 183 with a local diagnosis of idiopathic non-specific interstitial pneumonia (iNSIP) and 34 with a local diagnosis of idiopathic or Cryptogenic Organising Pneumonia (COP). Autoantibody status was determined by radio-immunoprecipitation. Results Overall, CTD-autoantibodies were identified in 15% of patients with a prior label of “idiopathic” ILD. CTD autoantibodies were more common in those with a prior diagnosis of COP, where more than 1 in 5 patient samples contained a potentially relevant autoantibody, see table. The autoantibodies identified included those readily detectable e.g. anti-Jo1, in addition to rarer antibodies not included in standard assays e.g. anti-EIF2B. Nearly half of all autoantibodies detected were anti-synthetase autoantibodies. Conclusion Covert CTD-ILD is potentially being missed as a diagnosis in patients who have been labelled by local teams as having idiopathic forms of inflammatory ILD (COP or iNSIP). More specific guidance on autoantibody testing and the interpretation of these test results could improve diagnosis and ensure patients receive more appropriate management. Disclosure S.L. Tansley: None. C.V. Cotton: None. F.K. McMorrow: None. H. Lu: None. Z.E. Betteridge: None. R.P. New: None. L.G. Spencer: None. N.J. McHugh: None. R.G. Cooper: None.

P223 Predictors of mortality in idiopathic inflammatory myopathy-associated interstitial lung disease - a systematic review and meta-analysis

Abstract Background/Aims Interstitial Lung Disease (ILD) affects approximately 30% of patients with idiopathic inflammatory myopathies (IIM). It is a leading cause of morbidity and mortality in IIM patients. Natural history of ILD varies widely from rapidly-progressive to indolent with minimal symptoms. IIM describes a collection of related autoimmune, inflammatory disorders predominantly affecting combinations of muscles, skin and lungs. Improving understanding of ILD clinical course will aid prognostication and guide sub-categorisation to improve future research in the field. We performed a systematic review and meta-analysis of prognostic factors in IIM-ILD. Methods MEDLINE and EMBASE databases were interrogated on 18/03/2021 using a pre-defined search protocol (PROSPERO ID:CRD42021240206). Studies providing summary data relating to numbers of survivors vs non-survivors according to any baseline criteria were selected. Baseline characteristics reported in ≥ 5 papers were included for meta-analysis. Risk of bias was assessed by Newcastle-Ottawa score. Stata-16 software was used for meta-analyses using a random effects model to report difference as odds ratio for binary variables, and hedge’s g standardised mean difference for continuous variables. A continuity correction was applied for zero effect studies. Heterogeneity was measured by I2, and publication bias assessed with Egger’s test. Results The search returned 4211 articles. 722 were relevant for abstract review, with 454 requiring full text assessment. 78 studies were eligible for inclusion. Overall mortality was 26.1% (+/-0.14 SD). 62 studies were from Asia, two from Mexico and four from Europe, with mortality rates of 26.5%, 13.6% and 25.3% respectively. The strongest risk factor is anti-MDA-5 antibody (OR 6.03). Conversely anti-tRNA-synthetase antibodies (ARS) are protective. When ARS+ was compared to MDA-5-/ARS- patients only, this difference between the groups disappeared. Anti-MDA-5 titre showed a non-significant effect direction towards higher mortality. ANA, anti-SS-A/Ro52 did not significantly impact mortality. Clinical predictors of increased mortality were male gender, acute/sub-acute onset, clinically amyopathic disease (CADM), dyspnoea, ulceration, fever and increasing age. Additional investigations shown to positively predict mortality were CRP, ferritin, LDH, AaO2 gradient, ground glass opacity and fibrosis HRCT scores. Whereas higher SP-D, lymphocytes, %FVC and %DLCO were protective. Conclusion Whilst many factors were associated with increased mortality in IIM-ILD, heterogeneity between studies is high with all having moderate to high risk of bias. A majority of the data come from studies in Japanese and Chinese populations where anti-MDA5 disease appears to be particularly prevalent and associated with deleterious outcomes. Extrapolating to local populations may not be appropriate. The domination of studies by anti-MDA5 disease may be masking risk factors relevant to other IIM subgroups. Due to the rarity of IIMs, these subgroups are often researched together, however this meta-analysis highlights the need to better categorise IIM patients in clinical research. Disclosure J.R. Hannah: None. T. Gordon: None. M. Rooney: None. J. Galloway: None. P. Gordon: None.

Care patterns of patients with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype

BackgroundInterstitial lung diseases (ILDs) include a variety of parenchymal lung diseases. The most common types of ILDs are idiopathic pulmonary fibrosis (IPF), autoimmune ILDs and hypersensitivity pneumonitis (HP). There is limited real world data on care patterns of patients with chronic fibrosing ILDs with a progressive phenotype other than IPF. Therefore, the aim of this study is to describe care patterns in these patients.MethodsThis retrospective cohort study used claims data from 2015 to 2019 from the Optum Research Database. The study population included adults (≥ 18 years old) with at least two diagnosis codes for fibrosing ILD during the identification period (1OCT2016 to 31DEC2018). A claim-based algorithm for disease progression was used to identify patients likely to have a progressive fibrotic phenotype using progression proxies during the identification period. Index date was the first day of progression proxy identification after fibrosing ILD diagnosis. Patients were required to have continuous enrollment for 12 months before (baseline) and after (follow-up) index date. Patients with an IPF diagnosis were excluded. Descriptive statistics were used to describe the patient population and care patterns.Results11,204 patients were included in the study. Mean age of the patient population was 72.7 years, and 54.5% were female. Unclassified ILDs (48.0%), HP (25.2%) and autoimmune ILDs (16.0%) were the most common ILD types. Other respiratory conditions were prevalent among patients including chronic obstructive pulmonary disease (COPD) (58.9%), obstructive sleep apnea (OSA) (25.0%) and pulmonary hypertension (9.8%). During baseline, 65.3% of all patients had at least one pulmonology visit, this proportion was higher during follow-up, at 70.6%. Baseline and follow-up use for HRCT were 39.9% and 48.8%, and for pulmonary function tests were 43.7% and 48.5% respectively. Use of adrenal corticosteroids was higher during follow-up than during baseline (62.5% vs. 58.0%). Anti-inflammatory and immunosuppressive medication classes were filled by a higher percentage of patients during follow-up than during baseline.ConclusionsComprehensive testing is essential for diagnosis of a progressive phenotype condition, but diagnostic tests were underutilized. Patients with this condition frequently were prescribed anti-inflammatory and immunosuppressive medications.

Myositis-specific autoantibodies in clinical practice: Improving the performance of the immunodot

Background/objectivesIdiopathic inflammatory myopathies (IIM) diagnosis and sub-classification can be improved by detection of myositis specific antibodies (MSA) as a first step in diagnosis. However, when using semi-quantitative immunodots for MSA detection, clinical assay performance needs to be improved. MethodsA retrospective study was done for the “myositis” and “synthetase” immunodots (SRP, NXP2, TIF1gamma, SAE1/2, Mi2, MDA5, Jo1, PL7, PL12, EJ, OJ, KS, ZO and HA) from D-Tek used for 270 patients who had tested positive for MSA in a tertiary laboratory hospital. ResultsResults from this analysis revealed: (i) none of the 60 healthy controls presented MSA; (ii) a low assay specificity among patients who tested positive for MSA, 128/270 (47%) were labeled IIM based on the manufacturer's recommended threshold; (iii) in non-IIM patients (53%), the MSA spectrum overlaps predominantly with other autoimmune diseases or idiopathic interstitial lung disease; and (iv) use of a clinical cut-off improves assay specificity for anti-SRP, anti-NXP2, anti-MDA5, anti-Jo1 and anti-PL7 Abs. ConclusionDetermining the clinical threshold of the semi-quantitative immunodot assay for MSA is effective for improving its capacity to discriminate IIM from non-IIM and, when IIM diagnosis is excluded, another autoimmune disease or an idiopathic interstitial lung disease should be considered in front of a positive MSA.

Cryptogenic Organizing Pneumonia Obscured by a Presumed COVID-19 Pneumonia: A Case Report

Interstitial lung disease (ILD) is a group of more than 200 conditions with various etiologies that result in a wide range of inflammation and/or fibrosis of the pulmonary interstitium. Cryptogenic Organizing Pneumonia (COP) is a type of idiopathic ILD that requires a high index of suspicion with an appropriate workup to make the diagnosis. The Coronavirus Disease 2019 (COVID-19) pandemic has enabled COVID-19 pneumonia to become a top differential diagnosis, which has consequently introduced bias into medical decision-making. We present a case of COP that was misdiagnosed for COVID-19 pneumonia for months despite several negative COVID-19 test results. This case also raises awareness of the cognitive bias that likely allowed for the misdiagnosis, resulting in delayed appropriate treatment for this patient.

CDKN2B antisense RNA 1 expression alleviates idiopathic pulmonary fibrosis by functioning as a competing endogenouse RNA through the miR-199a-5p/Sestrin-2 axis

ABSTRACT Idiopathic pulmonary fibrosis (IPF) is an idiopathic interstitial lung disease. At present, the pathogenesis of IPF has not been fully elucidated, which has affected the development of effective treatment methods. Here, we explored the function and potential mechanism of long noncoding RNA (lncRNA) CDKN2B antisense RNA 1 (CDKN2B-AS1) in IPF.Transforming growth factor-β (TGF-β) and bleomycin (BLM) were used to induce IPF in cells and animal models. Real Time quantitative Polymerase Chain Reaction (RT-qPCR) showed the expression of CDKN2B-AS1, miR-199a-5p and Sestrin-2 (SESN2) in cells and tissues. The double luciferase reporter gene assay confirmed the targeting relationship among CDKN2B-AS1, miR-199a-5p, and SESN2. Related protein levels were detected by Western blot combined with Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry to analyze cell proliferation, migration, and apoptosis. The pathological characteristics of mouse lung tissue were determined by Hematoxylin-eosin (HE) and Masson staining. We found that the expression of CDKN2B-AS1 was decreased in TGF-β-treated cells and BLM-treated mice. Overexpression of CDKN2B-AS1 inhibited cell proliferation and migration, promoted apoptosis, decreased the expression of fibrosis-related proteins and promoted autophagy. In addition, overexpression of CDKN2B-AS1 alleviated pulmonary fibrosis in BLM-treated mice. Mechanistically, CDKN2B-AS1 acts as a miR-199a-5p sponge to regulate SESN2 expression. Our results indicate the importance of the CDKN2B-AS1/miR-199a-5p/SESN2 axis.

A Handcrafted Radiomics-Based Model for the Diagnosis of Usual Interstitial Pneumonia in Patients with Idiopathic Pulmonary Fibrosis.

The most common idiopathic interstitial lung disease (ILD) is idiopathic pulmonary fibrosis (IPF). It can be identified by the presence of usual interstitial pneumonia (UIP) via high-resolution computed tomography (HRCT) or with the use of a lung biopsy. We hypothesized that a CT-based approach using handcrafted radiomics might be able to identify IPF patients with a radiological or histological UIP pattern from those with an ILD or normal lungs. A total of 328 patients from one center and two databases participated in this study. Each participant had their lungs automatically contoured and sectorized. The best radiomic features were selected for the random forest classifier and performance was assessed using the area under the receiver operator characteristics curve (AUC). A significant difference in the volume of the trachea was seen between a normal state, IPF, and non-IPF ILD. Between normal and fibrotic lungs, the AUC of the classification model was 1.0 in validation. When classifying between IPF with a typical HRCT UIP pattern and non-IPF ILD the AUC was 0.96 in validation. When classifying between IPF with UIP (radiological or biopsy-proved) and non-IPF ILD, an AUC of 0.66 was achieved in the testing dataset. Classification between normal, IPF/UIP, and other ILDs using radiomics could help discriminate between different types of ILDs via HRCT, which are hardly recognizable with visual assessments. Radiomic features could become a valuable tool for computer-aided decision-making in imaging, and reduce the need for unnecessary biopsies.

El informe radiológico en patología intersticial pulmonar

Interstitial lung disease, also known as diffuse parenchymal lung disease, comprises a broad group of acute and chronic conditions, some of which have known causes and others whose cause remains to be determined. The most common of these conditions are idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis, and interstitial lung diseases associated with collagen vascular diseases. Although plain-film chest X-rays remain useful in the diagnosis of these diseases, they are difficult to interpret and have low diagnostic sensitivity. Thus, high-resolution computed tomography (CT) is the technique of choice for their diagnosis.The definitive diagnosis of interstitial lung disease should be reached through a consensus among clinicians, radiologists, and pathologists, so the radiology report is an essential part of the diagnostic process. The report must be clear and succinct, providing basic information including the imaging findings, the differential diagnosis, and, when necessary, information about the most appropriate lung areas for biopsy.We review the role of the radiological report in interstitial lung disease, including the structured report.

Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease.

In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P < 0.01) and anti-Jo1 (64.9%, P < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P < 0.05). Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.

The use of exhaled air analysis in discriminating interstitial lung diseases: a pilot study

BackgroundFibrotic Interstitial lung diseases (ILD) are a heterogeneous group of chronic lung diseases characterized by diverse degrees of lung inflammation and remodeling. They include idiopathic ILD such as idiopathic pulmonary fibrosis (IPF), and ILD secondary to chronic inflammatory diseases such as connective tissue disease (CTD). Precise differential diagnosis of ILD is critical since anti-inflammatory and immunosuppressive drugs, which are beneficial in inflammatory ILD, are detrimental in IPF. However, differential diagnosis of ILD is still difficult and often requires an invasive lung biopsy. The primary aim of this study is to identify volatile organic compounds (VOCs) patterns in exhaled air to non-invasively discriminate IPF and CTD-ILD. As secondary aim, the association between the IPF and CTD-ILD discriminating VOC patterns and functional impairment is investigated.MethodsFifty-three IPF patients, 53 CTD-ILD patients and 51 controls donated exhaled air, which was analyzed for its VOC content using gas chromatograph- time of flight- mass spectrometry.ResultsBy applying multivariate analysis, a discriminative profile of 34 VOCs was observed to discriminate between IPF patients and healthy controls whereas 11 VOCs were able to distinguish between CTD-ILD patients and healthy controls. The separation between IPF and CTD-ILD could be made using 16 discriminating VOCs, that also displayed a significant correlation with total lung capacity and the 6 min’ walk distance.ConclusionsThis study reports for the first time that specific VOC profiles can be found to differentiate IPF and CTD-ILD from both healthy controls and each other. Moreover, an ILD-specific VOC profile was strongly correlated with functional parameters. Future research applying larger cohorts of patients suffering from a larger variety of ILDs should confirm the potential use of breathomics to facilitate fast, non-invasive and proper differential diagnosis of specific ILDs in the future as first step towards personalized medicine for these complex diseases.

Management of cough in patients with idiopathic interstitial lung diseases in primary care.

Importance: Cough is a common symptom in idiopathic interstitial lung diseases (ILDs), there is little information of its management in primary care. The objective of this study was to explore the frequency of cough-related consultations and the medications prescribed to patients with ILDs in primary care. Methods: This retrospective cohort study used electronic medical records (EMR) from Manitoba primary care providers participating in the Manitoba Primary Care Research Network repository (2014–2019). Cough-related consults and the subsequent medications prescribed to patients with ILDs were identified in the EMR. Results: 295 patients with ILDs were identified, 73 (25%) of them had 141 cough-related consultations (mean 1.9, SD 1.3) during the period studied. In 50 (35%) of the consultations, patients were prescribed one or more of the following: inhaled bronchodilators (34%), nasal corticoids (18%), codeine/opiates (18%), antibiotics (14%), inhaled corticoids (14%), proton pump inhibitors (8%), cough preparations (6%), antihistamines (4%), and oral corticoids (2%). 13 (26%) subsequent cough-related consultations were identified within 6 months, mainly among patients who were prescribed cough preparations, nasal corticoids, antihistamines, and antibiotics. Conclusion: One-quarter of patients with ILDs consulted primary care due to cough, and about a third of them received a prescription to address potentially underlying causes of cough. Although further studies are required to explore the effect of the medications prescribed, recurrent cough consultations suggested that cough preparations, nasal corticoids, and antihistamines are among the least effective treatments. More research is needed to understand the causes and optimal treatment of cough in patients with ILDs.

The prognostic value of the COPD Assessment Test in fibrotic interstitial lung disease.

The COPD Assessment Test (CAT) has been studied as a measure of health status in idiopathic pulmonary fibrosis (IPF) and interstitial lung disease associated with connective tissue disease. However, its prognostic value is unknown. The present study explored the association between CAT score and mortality in fibrotic interstitial lung disease (FILD), including IPF and other forms of ILD. We retrospectively analyzed 501 consecutive patients with FILD who underwent clinical assessment, including pulmonary function test and CAT. The association between CAT score and 3-year mortality was assessed using Cox proportional hazard analysis, Kaplan-Meier plots, and the log-rank test for trend. To handle missing data, the imputed method was used. The patients' median age was 68 years, and 320 were male (63.9%). Regarding CAT severity, 203 patients had a low impact level (score <10), 195 had a medium level (10-20), 80 had a high level (21-30), and 23 had a very high level (31-40). During the 3-year study period, 118 patients died. After adjusting for age, sex, forced vital capacity, diffusion capacity for carbon monoxide, IPF diagnosis, and usual interstitial pneumonia pattern on high-resolution computed tomography, the CAT score was significantly associated with 3-year mortality (hazard ratio in increments of 10 points: 1.458, 95% confidence interval 1.161-1.830; p<0.001). In addition, patients with high and very high impact levels had twofold and threefold higher mortality risk than those with low levels, respectively. The CAT has prognostic value in FILD.

Interstitial pneumonia with autoimmune features: Evaluation of connective tissue disease incidence during follow-up

ObjectivesAmong interstitial pneumonia with autoimmune features (IPAF) patients, identifying those at risk to develop a connective tissue disease (CTD) during the disease course is a key issue. The aim of this study was to evaluate the incidence of definite CTD diagnosis in IPAF patients during follow-up. MethodsWe performed a multicentric cohort study of interstitial lung disease (ILD) from 2010 to 2017 in pneumology and immunology departments of tertiary care centers. Patients with a known cause of ILD (including established CTD) at diagnosis were excluded. Among patients with idiopathic ILD and at least three years of follow-up, two groups (IPAF and non-IPAF) were retrospectively analyzed at time of diagnosis. ResultsA total of 249 patients with ILD were enrolled, including 70 IPAF and 179 non-IPAF patients. After a mean follow-up time of 77 ± 44 months, 18/70 IPAF patients (26%) had a CTD diagnosis – 9 antisynthetase syndrome, 8 systemic sclerosis and 1 overlap myositis – compared with 4/179 non-IPAF patients (2%). IPAF patients were at higher risk of CTD occurrence at 3 years of follow-up compared to non-IPAF patients (HR 10.1, 95% CI 3.1–33.1, p < 0. 01). IPAF patients progressing to CTD tended to be younger, more often female and have more frequently puffy fingers, capillaroscopy abnormalities and antisynthetase antibodies at diagnosis. ConclusionsWe found that a significant proportion of IPAF patients had associated CTD diagnosis during follow-up. Prospective studies are needed to confirm baseline predictive factors of CTD occurrence in IPAF patients.

Antitussive Effect of a Chest Band in Patients with Interstitial Lung Disease: The Preliminary Results from a Pre-post Intervention Study.

Objective Evidence supporting the efficiency of clinically administered therapies against interstitial lung disease (ILD)-related cough is limited. Thus, we conducted a study to evaluate the efficacy of short-term use of chest bands on cough in patients with ILD. Methods This pre-post intervention study was performed at two university hospitals between April 2017 and August 2020. Scores of the visual analog scale (VAS) for cough severity (in terms of frequency and intensity), Leicester Cough Questionnaire (LCQ)-acute, and frequency scale for symptoms of gastroesophageal reflux disease (FSSG) were assessed before and after the use of the chest band (24/48 hours). Patients The study included patients with idiopathic interstitial pneumonias (IIPs) or connective tissue disease-associated interstitial lung disease (CTD-ILD). Results Four patients with IIPs and seven with CTD-ILD were included in the analysis. The cough intensity and LCQ-acute total score improved significantly after the use of the chest band (p=0.007 and p=0.005, respectively), although the cough frequency showed no significant reduction (p=0.074). Furthermore, the FSSG total and acid-reflux symptom scores improved (p=0.018 and p=0.027, respectively), and a negative correlation between the change in LCQ-acute total score and that in FSSG score for acid-reflux symptoms was observed (Spearman rho =-0.841, p=0.001). Conclusion The results of the current study suggest that chest bands might be useful for treating chronic refractory cough in patients with ILD and gastroesophageal reflux disease. However, these results should be interpreted with caution due to methodological limitations associated with this study.

The Extent of Honeycombing on Computed Tomography Cannot Predict the Treatment Outcome of Patients with Acute Exacerbations of Interstitial Lung Disease.

Background The purpose of this retrospective study was to clarify whether the presence of honeycombing on computed tomography (CT) can affect the prognosis of patients with acute exacerbations (AEs) of interstitial lung diseases (ILDs). Methods Clinical parameters including age, sex, Charlson Comorbidity Index Score (CCIS), blood biomarkers, and 3-month mortality were retrospectively compared between the CT honeycombing present and absent groups at the diagnosis of AEs of ILDs. Results Ninety-five patients who were on corticosteroid pulse therapy were assessed. Though log-rank tests showed that Kaplan–Meier survival curves of the high and low ground-glass opacity (GGO) score groups differed significantly in 3-month mortality in patients with AEs of idiopathic ILDs (P = 0.007) and overall patients (P = 0.045), there was no significant difference between the CT honeycombing present and absent groups in patients with AEs of idiopathic ILDs (P = 0.472) and AEs of secondary ILDs (P = 0.905), as well as of overall patients (P = 0.600). In addition, whereas CCIS (OR, 1.436; 95% CI, 1.156–1.842; P < 0.001) was a significant predictor of 3-month mortality in the CT honeycombing absent group, serum LDH (OR, 1.005; 95% CI, 1.002–1.007; P = 0.001) was a significant predictor in the CT honeycombing present group. Conclusions The clinical features of patients with or without honeycombing may differ due to the difference in prognostic factors, but these groups were found to have similar prognoses 3 months after AE onset, and clinicopathological examinations according to these groups are essential.

GAP Score and CA-153 Associated with One-Year Mortality in Anti-MDA-5 Antibody-Positive Patients: A Real-World Experience.

Background. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. Methods. We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up. Results. A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality. Conclusions. Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management.

Prognostic value of radiological findings indeterminate for UIP pattern and anterior upper lobe honeycomb-like lesion in chronic fibrosing interstitial lung disease associated with MPO-ANCA

BackgroundMyeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is often positive in patients with interstitial lung disease (ILD), which is also often present in patients with microscopic polyangiitis (MPA). A possible association between MPO-ANCA, MPA, and idiopathic ILD remains unclear. The objective of this study was to determine whether high-resolution computed tomography (HRCT) classification based on recent idiopathic pulmonary fibrosis guideline and specific CT findings can obtain new knowledge of prognostic factors in all MPO-ANCA-positive patients with ILD including both idiopathic ILD and MPA-ILD.MethodsWe analyzed 101 consecutive MPO-ANCA-positive patients with respiratory disease. We assessed the diagnostic accuracy of CT findings, HRCT pattern, and specific radiological signs. Prognostic predictors were determined using Cox regression models.ResultsSubjects with chronic ILD included 22 patients with MPA-ILD and 39 patients with ILD but without MPA. A quarter of the patients were radiological indeterminate for usual interstitial pneumonia (UIP) pattern, which resulted in a better prognosis than that for UIP pattern. “Increased attenuation around honeycomb and traction bronchiectasis” and “anterior upper lobe honeycomb-like lesion” were found to be highly frequent radiological findings (39% and 30%, respectively). In addition, the latter finding was a significant negative prognostic factor.ConclusionsRadiological indeterminate for UIP was a useful HRCT classification in MPO-ANCA-positive patients with ILD. In addition, anterior upper lobe honeycomb-like lesion was found to be specific radiological finding that was a significant prognostic factor. The present results might aid in the assessment of appropriate strategies of diagnosis in these patients.