Including Interstitial Lung Disease Research Articles

Abstract PO3-12-04: Pulmonary Complication related to Trastuzumab Deruxtecan. A pharmacovigilance study from 2022-2023 FAERS Database

Abstract Background: The horizon of Trastuzumab Deruxtecan (T-DXd), an antibody-drug conjugate, has been expanding. After its promising results in HER2-positive/HER2-low Breast cancer, it has been on trial for other cancers, such as HER2-negative breast cancers, Gastrointestinal, lung, colorectal, urothelial, etc., and it has shown promising results in clinical trials. However, there have been reports of pulmonary adverse events associated with T-DXd, including interstitial lung disease (ILD) and pneumonitis. Understanding the occurrence and characteristics of these pulmonary complications is essential for optimizing patient care and ensuring the safe use of T-DXd. Using the FAERS (FDA Adverse Event Reporting System) database for 2022-2023 aims to see T-DXd-related pulmonary complications and guide healthcare professionals in monitoring and managing these adverse events effectively. Methods: We conducted a retrospective analysis of all reported cases of respiratory complications in patients using TDXD, utilizing data reported to the FDA Adverse Event Reporting System (FAERS) database for January 2022 to March 2023. We included patients of more than 18; these cases were identified and classified using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Results: In this study, a total of 296 cases of adverse events were reported in patients using TDXD. Among these cases, 74 (27%) were respiratory adverse events. The most frequently observed respiratory complications were interstitial lung disease (ILD) and pneumonitis, with 21 cases each, accounting for 56% of the total respiratory complications. Out of the 14 reported deaths in this cohort, pneumonitis was the most commonly seen respiratory complication, occurring in 8 patients, followed by pulmonary embolism and ILD, each reported in 4 patients. Conclusion: Respiratory complications were the most frequent among the reported adverse events, accounting for 27% of all cases. ILD and pneumonitis were the most common complications, with 14 deaths reported in this group. These findings underline the importance of closely monitoring and managing pulmonary adverse events in patients treated with T-DXd. Healthcare professionals can use this information to optimize patient care and ensure the safe use of T-DXd. However, it is important to note that this study was based on a database and has limitations such as underreporting bias and lack of a control group, which hinders establishing a causal relationship. Additional research is needed to identify risk factors and improve patient outcomes. Citation Format: Niraj Neupane, Himal Kharel, Sangharsha Thapa. Pulmonary Complication related to Trastuzumab Deruxtecan. A pharmacovigilance study from 2022-2023 FAERS Database [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-04.

Clinical improvement in early onset interstitial lung disease using rituximab in children with anti-MDA5 positive juvenile dermatomyositis.

Children with juvenile dermatomyositis (JDM) and antibodies to melanoma differentiation associated gene 5 (anti-MDA5) are at increased risk of severe disease complications, including interstitial lung disease (ILD). Data regarding treatment of disease complications in this patient population is limited. In this study, we examined the disease course of children with JDM and anti-MDA5 antibodies before and after treatment with rituximab (RTX). Patients (age 2-21 years) seen at the Children's Hospital at Montefiore between July 2012 and August 2021, with a diagnosis of JDM, positive anti-MDA5 positive antibodies, evidence of ILD, and who were treated with rituximab were eligible for inclusion. Retrospective clinical and laboratory data were reviewed. Five out of 8 patients with positive anti-MDA5 antibodies had evidence of ILD (62.5%). Four patients had data available for review. All patients received at least 5 courses of RTX infusions, with discontinuation of steroids by an average of 12 months after starting RTX and a decrease to fewer than two concurrent medications by fifth course of RTX. Indicators of ILD on high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) either improved or fully resolved over the course of RTX treatment for all patients. Patients also demonstrated resolution of active cutaneous manifestations and musculoskeletal disease activity. This is the first study to examine the use of RTX in children with JDM and anti-MDA5 antibodies, with notable improvements ILD, cutaneous and musculoskeletal manifestations. Further studies are needed to better understand the efficacy of RTX on JDM disease related complications.

Atypical Presentation of Antisynthetase Syndrome: A Case Report

ABSTRACT Antisynthetase syndrome is characterized by autoantibodies against one of many aminoacyl transfer RNA synthetases. The clinical features include interstitial lung disease (ILD), non-erosive arthritis, Raynaud’s phenomenon, myositis, unexplained fever, and/or mechanic’s hands. There is higher incidence of ILD compared to polymyositis or dermatomyositis. Antisynthetase syndrome associated with Pl-7 and Pl-12 antibodies is rare and accounts for less than 10% of all cases. We present a case of 63-year-old lady who presented with only polymyositis without any ILD or other features of antisynthetase syndrome and was positive for anti Pl-7 and anti Pl-12 antibodies.

Anti-synthetase syndrome-associated interstitial lung disease possibly caused by atezolizumab in a patient with lung adenocarcinoma: a case report

BackgroundAnti-aminoacyl-tRNA synthetase (ARS) antibody-positive patients present with a variety of symptoms, including interstitial lung disease (ILD), which is termed anti-synthetase syndrome (ASS). But it is rare that ASS-ILD is considered an immune-related adverse event after the use of immune checkpoint inhibitors (ICIs).Case presentationA 47-year-old male with advanced lung adenocarcinoma was treated with platinum and ICI combination immunotherapy and was followed up as an outpatient. Nine months after the start of treatment, he developed a fever and cough, and imaging findings showed lung consolidations in the bilateral lower lung fields. The patient was positive for anti- ARS antibodies and was considered to have developed ASS-ILD due to ICIs remitted with steroid therapy. The patient was found to be positive for anti-ARS antibodies before ICI administration, and the antibody titer was elevated compared to that before ICI administration.ConclusionsThe examination of anti-ARS antibodies pior to the administration of ICIs may be useful in predicting the development of ASS-ILD.

Upper respiratory tract mycobiome alterations in different kinds of pulmonary disease.

The human respiratory tract is considered to be a polymicrobial niche, and an imbalance in the microorganism composition is normally associated with several respiratory diseases. In addition to the well-studied bacteriome, the existence of fungal species in the respiratory tract has drawn increasing attention and has been suggested to have a significant clinical impact. However, the understanding of the respiratory fungal microbiota (mycobiome) in pulmonary diseases is still insufficient. In this study, we investigated the fungal community composition of oropharynx swab (OS) samples from patients with five kinds of pulmonary disease, including interstitial lung disease (ILD), bacterial pneumonia (BP), fungal pneumonia (FP), asthma (AS) and lung cancer (LC), and compared them with healthy controls (HCs), based on high-throughput sequencing of the amplified fungal internal transcribed spacer (ITS) region. The results showed significant differences in fungal composition and abundance between disease groups and HCs. Malassezia was the most significant genus, which was much more abundant in pulmonary diseases than in the control. In addition, many common taxa were shared among different disease groups, but differences in taxa abundance and specific species in distinct disease groups were also observed. Based on linear discriminant analysis effect size (LefSe), each group had its characteristic species. Furthermore, some species showed a significant correlation with the patient clinical characteristics. Our study deepened our understanding of the respiratory tract mycobiome in some diseases that are less studied and identified the commonalities and differences among different kinds of pulmonary disease. These results would provide the solid basis for further investigation of the association between the mycobiome and pathogenicity of pulmonary diseases.

Methotrexate-related adverse events and impact of concomitant treatment with folic acid and tumor necrosis factor-alpha inhibitors: An assessment using the FDA adverse event reporting system.

Methotrexate (MTX) is an essential anti-rheumatic drug used to treat rheumatoid arthritis (RA). Prevention or management of adverse reactions, including interstitial lung disease (ILD), hepatotoxicity, myelosuppression, and infection, remains fundamental for safe MTX therapy. Using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) (JAPIC AERS), we performed disproportionality analyses of adverse events related to MTX use and the impact of concomitant medications. Upon analyzing all reported cases in FAERS between 1997 and 2019, the crude reporting odds ratios (cRORs; 95% confidence intervals) for ILD, hepatotoxicity, myelosuppression, and tuberculosis (TB) in relation to MTX use were 4.00 (3.83-4.17), 1.99 (1.96-2.02), 3.66 (3.58-3.74), and 7.97 (7.65-8.3), respectively. Combining MTX with folic acid (FA) or tumor necrosis factor-alpha inhibitors (TNFis) tended to reduce cRORs for these adverse events (except for TB). Multiple logistic regression analysis in patients with RA was conducted to calculate adjusted reporting odds ratios (aRORs) for age, sex, and MTX treatment patterns (MTX alone and combined with FA and TNFi). Higher age (except for hepatotoxicity) and male sex were significantly associated with adverse events. Combining FA or TNFi with MTX reduced aRORs for MTX-related hepatotoxicity and myelosuppression; in contrast, the effect of FA was not obvious in ILD or TB. Although studies assessing spontaneous reporting systems have limitations such as reporting bias, data from our logistic regression analysis demonstrated that adding FA to MTX-based therapy could help reduce the dose-dependent adverse events of MTX, thereby providing clinical evidence that supports the beneficial effect of FA. This study also demonstrated the usefulness of FAERS in comparing adverse events based on treatment patterns.

Antibodies against Serum Anti-Melanoma Differentiation-Associated Gene 5 in Rheumatoid Arthritis Patients with Chronic Lung Diseases

Chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway diseases (ADs), are common complications of rheumatoid arthritis (RA). Rheumatoid factor (RF) and anti-citrullinated peptide antibodies are reported to be associated with CLD in RA patients. The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies (Abs) is associated with clinically amyopathic dermatomyositis developing into rapidly progressive ILD. However, few studies on anti-MDA5 Abs in RA have been published. Here, we analyzed the association of anti-MDA5 Abs with CLD complications in RA. Anti-MDA5 Abs were quantified in sera from RA patients with or without CLD. Anti-MDA5 Ab levels were higher in RA patients with ADs than without (mean ± SDM, 4.4 ± 2.4 vs. 4.0 ± 4.2, p = 0.0001). AUC values of anti-MDA5 Ab and RF ROC curves were similar in RA patients with or without CLD (0.578, 95%CI 0.530-0.627 and 0.579, 95%CI 0.530-0.627, respectively, p = 0.9411). Multiple logistic regression analysis of anti-MDA5 Abs and clinical characteristics yielded an MDA5-index with a higher AUC value than anti-MDA5 Ab alone (0.694, 95%CI 0.648-0.740, p = 5.08 × 10-5). Anti-MDA5 Abs were associated with ADs in RA patients and could represent a biomarker for CLD, similar to RF. The involvement of anti-MDA5 Abs in the pathogenesis of ADs in RA is proposed.

Tomographic pleuropulmonary manifestations in rheumatoid arthritis: a pictorial essay.

Rheumatoid arthritis (RA) is an autoimmune inflammatory and heterogeneous disease that affects several systems, especially the joints. Among the extra-articular manifestations of RA, pleuropulmonary involvement occurs frequently, with different presentations, potentially in all anatomic thoracic compartments, and may determine high morbidity and mortality. The most common pleuropulmonary manifestations in patients with RA include interstitial lung disease (ILD), pleural disease, pulmonary arterial hypertension, rheumatoid lung nodules, airway disease (bronchiectasis and bronchiolitis), and lymphadenopathy. Pulmonary hypertension and ILD are the manifestations with the greatest negative impact in prognosis. HRCT of the chest is essential in the evaluation of patients with RA with respiratory symptoms, especially those with higher risk factors for ILD, such as male gender, smoking, older age, high levels of rheumatoid factor, or positive anti-cyclic citrullinated peptide antibody results. Additionally, other etiologies that may determine tomographic pleuropulmonary manifestations in patients with RA are infections, neoplasms, and drug-induced lung disease. In these scenarios, clinical presentation is heterogeneous, varying from being asymptomatic to having progressive respiratory failure. Knowledge on the potential etiologies causing tomographic pleuropulmonary manifestations in patients with RA coupled with proper clinical reasoning is crucial to diagnose and treat these patients.

LUNG DAMAGE AS A COMPLICATION OF SYSTEMIC JUVENILE ARTHRITIS

According to modern science, systemic juvenile arthritis (sJA) is an autoinflammatory disease characterized by severe systemic manifestations and life-threatening complications. This article discusses the developmental predictors, clinical and radiological manifestations and pathogenetic features of the disease. Particular attention is paid to genetically engineered biological therapy.
 Numerous pulmonary complications are now known in sJA children, including interstitial lung disease (ILD), pulmonary alveolar proteinosis (PAP), pulmonary hypertension (PH), and lipoid pneumonia. Fatality rate in sJA patients increases against the macrophage activation syndrome (MAS) development and pulmonary hypertension, which occurs with proliferation of endothelial cells, muscle tissue and fibroblasts in the lungs vessels. A more severe disease progression is typical for children with genetic defects. SAM and PAP relapses are observed more often in such patients. Instrumental diagnostic methods helped to identify, 5 subtypes determining the lung tissue damage in sJA. Computer tomography (CT) revealed the main signs of lung damage in sJA patients: ground-glass opacity, crazy-paving sign, thickening of the bronchial wall, interlobar septum, pleura, peripheral consolidation, and lymphadenopathy. Due to the high level of sJA activity, children were prescribed genetically engineered biological drugs (GEBP). Timely therapeutic correction is necessary to exclude life-threatening adverse reactions. Under dynamic observation, it is possible to diagnose lung damage in children at the early stage and to control the pathology.
 The purpose of this review is to systematize the existing data on developmental predictors, pathogenetic features of the disease, sJA clinical and radiological manifestations, and genetically engineered biological therapy as a method of sJA treatment.

Screening and characterization of myositis-related autoantibodies in COVID-19 patients.

An efficient host immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) appears to be crucial for controlling and resolving this viral infection. However, many studies have reported autoimmune characteristics in severe COVID-19 patients. Moreover, clinical observations have revealed that COVID-19-associated acute distress respiratory syndrome shares many features in common with inflammatory myopathy including interstitial lung disease (ILD), most particularly rapidly progressive (RP)-ILD. This study explored this phenomenon by seeking to identify and characterize myositis-specific and related autoantibodies in 25 COVID-19 patients with mild or severe symptoms. Line blot analysis with the EUROLINE Myopathies Ag kit identified 9 (36%) patients with COVID-19 with one or more autoantibodies against several myositis-related antigens (Jo-1, Ku, Mi-2β, PL-7, PL-12, PM-Scl 75, PM-Scl 100, Ro-52, and SRP); no anti-MDA5 antibodies were detected. As the presence of antibodies identified by line blots was unrelated to disease severity, we further characterized the autoantibodies by radioimmunoassay, in which [35 S]methionine-labeled K562 cellular antigens were precipitated and visualized by gel electrophoresis. This result was confirmed by an immunoprecipitation assay and immunoblotting; 2 patients exhibited anti-Ku70 and anti-Ku80 antibodies. Our data suggest that it is necessary to use more than one method to characterize and evaluate autoantibodies in people recovered from COVID-19, in order to avoid misinterpreting those autoantibodies as diagnostic markers for autoimmune diseases.

Comparing the effectiveness and safety of Abatacept and Tocilizumab in elderly patients with rheumatoid arthritis.

The number of biological DMARDs (bDMARDs) used in elderly patients with rheumatoid arthritis (RA) has increased in recent years. We aimed to compare the drug retention rates and safety of abatacept (ABT) and tocilizumab (TCZ) in elderly patients with RA. A total 125 elderly patients with RA (>65 years) who began therapy with either ABT (n = 47) or TCZ (n = 78) between 2014 and 2021 at our institute were enrolled. We compared the drug retention rate and clinical response at 24 weeks between elderly patients with RA treated with ABT and those treated with TCZ. Adverse events (AEs) and the reasons for drug discontinuation were assessed. There was no significant difference in demographic characteristics except for the use of glucocorticoid between the ABT and TCZ groups. There was no significant difference in the drug retention rate between the ABT and TCZ groups. Furthermore, there was no significant difference in the discontinuation rates due to the lack of effectiveness between these two groups. The proportions of the patients archiving low disease activity at 24 weeks did not differ significantly between the two groups. Whereas, the discontinuation rates due to AEs, including interstitial lung disease (ILD), seemed higher in the TCZ group than in the ABT group. In TCZ-treated group, the concomitant use of methotrexate (MTX) significantly increased the incidences of AEs leading to the discontinuation of TCZ. Whereas these was no significant impact of concomitant use of MTX on the incidences of AEs leading to discontinuation in ABT-treated group. In elderly patients with RA treated with ABT and TCZ, drug retention rates were equivalent between the two groups. There were some differences in safety profiles between ABT and TCZ, and the rates of discontinuation due to AEs, including ILD, seem to be lower with ABT than with TCZ in elderly patients with RA.

The associations between myositis autoantibodies and clinical presentations in dermatomyositis.

The myositis autoantibodies have been widely used clinically in recent years for the identification of an autoantibody-associated clinical phenotype in dermatomyositis (DM) patients. However, correlations between myositis autoantibodies and clinical presentations in different populations are lacking, especially in Taiwan. To investigate the correlations among cutaneous manifestations, myositis autoantibodies, and systemic diseases, including interstitial lung disease (ILD) and internal malignancy. A retrospective study of patients with histopathologically confirmed cutaneous manifestations of DM was conducted during 2005 to 2020 in Taiwan. A commercial line blot immunoassay technique was used to detect myositis autoantibodies. A total of 88 DM patients were enrolled, with a mean age of onset of 49.4 years old. The most common systemic features were myositis (56.8%, 50/88), internal malignancy (22.7%, 20/88), dysphagia (19.3%, 17/88), and ILD (17%, 15/88). Among the enrolled patients, 32 patients received serum myositis autoantibodies examination. The most common autoantibodies were ANA (50.7%, 37/73), followed by anti-TIF1-γ (34.4%, 11/32) and anti-MDA5 (31.3%, 10/32) antibodies. Patients with Gottron sign (OR 5.6), arthritis (OR 23.35), or the presence of anti-MDA5 antibody (OR 11.14) were more susceptible to progressing to ILD, whereas patients with pruritus (OR 1.04), dysphagia (OR 6.73), and the presence of ANA (OR 6.29) had significantly higher risks of developing internal malignancies. Physicians should pay special attention to certain clinical features, which can help with the early detection of systemic diseases. Cancer screening and myositis autoantibodies examination should be conducted in all DM patients if applicable.

014 Differential gene expression in lesional skin may signify immune-mediated lung parenchymal damage in dermatomyositis patients

Dermatomyositis (DM) is an autoimmune connective tissue disease that most commonly affects skin and muscles. Clinical manifestations can be protean, with some patients experiencing skin-limited disease while others develop serious systemic complications including interstitial lung disease (ILD). While both T cell-mediated and humoral immune dysregulation have been purported to play a role in manifesting said end-organ damage, our understanding of immunophenotypic prognostic factors associated with the development of ILD in DM patients remains limited.

Glandular involvement in primary Sjögren's syndrome patients with interstitial lung disease-onset and sicca-onset, a single centre cross-sectional study.

Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy classically presenting with sicca symptoms. Nonetheless, disease onset with extraglandular manifestations, including interstitial lung disease (ILD), is increasingly reported. However, studies investigating pSS patients presenting with ILD (pSS-ILD) are limited.Aim of this study was to better characterise the phenotype of pSS patients presenting with ILD in comparison to pSS patients with classicsicca-onset. We especially investigated whether the two groups differed in glandular involvement comparing functional, imaging andhistologic findings, as well as patient reported outcome (PRO). Consecutive newly diagnosed pSS patients, all fulfilling the ACR/EULAR 2016 criteria, were included in this cross-sectional study from September 2016 to October 2021. Presence of ILD at pSS diagnosis was defined based on clinical findings, imaging assessment and pulmonary function tests (PFT). In addition to functional tests, a minor salivary gland biopsy was performed in all cases, recording number of foci, focus score (FS) and GC-like structures. Salivary glands ultrasonography (SGUS) was graded using the OMERACT semiquantitative scoring system (0-3) based on parenchyma inhomogeneity. PRO including ESSPRI, OHIP and OSSDI were collected.Extraglandular clinical features and biological abnormalities included in the ESSDAI were recorded. Data were expressed as mean±SD for continuous variables and as absolute frequencies and percentages for categorical variables. Chi-Square test and Mann-Whitney U-test and ANOVA were performed for comparisons of categorical variables and continuous variables, respectively. We included 178 newly diagnosed pSS patients (F:M=158:20). ILD was the first pSS manifestation in 11 (6%) cases, 8 F and 3 M, with a median time from ILD onset to pSS diagnosis of 2 years (25-75 IQ 1-4.5). Of the 11 pSS-ILD patients, HRCT pattern was defined as NSIP in 4, UIP in 4, NSIP+OP in 2 and LIP in 1 patient. Dyspnoea on exertion or chronic cough were reported by 7/11 (63.6%) patients.In comparison to sicca-onset patients, pSS-ILD patients presented an older age at diagnosis (55±13 vs. 70±7, p= 0.001) and a higher ESSDAI (3.9±4.7 vs. 12.3±4.3, p=0.001), driven by the pulmonary domain. Regarding glandular involvement, pSS-ILD patients reported milder xeropthalmia (VAS 5.8±3.1 vs. 2.8±3.5, p=0.002) and significative lower scores in OSDI (35.6±24.9 vs. 15.3±22.9, p=0.04) and OHIP (4.8±4.4 vs. 1.4±3.8, p=0.04), despite no significant differences observed between the two groups in ocular tests and unstimulated salivary flow rate. With respect to histology, no significant differences were found in number of foci, FS and GC-like structures. We observed a significantly different distribution of the SGUS OMERACT score in the two groups: none of pSS-ILD patients presented a SGUS OMERACT score ≥2 in the submandibular glands (SG), in contrast to 41/132 (31.1%) of the patients in the classical sicca-onset group (p=0.03). Finally, no significant differences were observed between the two groups with respect to non-pulmonary extraglandular manifestations, serologic features and other biological parameters. ILD-onset pSS patients represent an atypical phenotypic subset, with less pronounced sialadenitis structural changes in salivary glands, and with sicca symptoms probably overshadowed by the respiratory disease.

Multidisciplinary Care and Prognosis in Patients With COPD and Interstitial Lung Disease Prescribed Long-Term Oxygen Therapy.

Home oxygen therapy is prescribed for patients with advanced lung disease based on the criteria established in landmark trials in subjects with COPD. In clinical practice, its use has been extrapolated to other diseases, including interstitial lung disease (ILD). Patients with COPD and ILD experience a high symptom burden and require access to specialized multidisciplinary care. We aimed to evaluate the health-related outcomes and supportive care needs of patients with COPD and ILD receiving home oxygen therapy. This was a retrospective cohort study using the oxygen database of a quaternary metropolitan teaching hospital. Patients with a diagnosis of COPD or ILD who were prescribed home oxygen therapy between January 2012-December 2018 were identified. Demographic information, results of physiologic testing, comorbidities, hospitalizations, and mortality data were collected. Three hundred and eighty-four subjects were included for analysis, of whom 56% were male. The median age was 75 y. The majority (59%) had a diagnosis of COPD. Long-term oxygen therapy (LTOT) was prescribed for 187 (48.7%), with no significant demographic differences between those with COPD or ILD. Another 187 were prescribed ambulatory oxygen alone, with 55 transitioning to LTOT during the study period. Most subjects (65.4%) were referred for pulmonary rehabilitation; however, palliative care referrals were generally low (22.9%). Referrals to other medical specialties and allied health were common (82%). Transplant-free survival after commencement of LTOT was poor, with 38% of subjects surviving at 5 y. The 5-y survival of subjects with ILD after commencing on LTOT was 10% compared to 52% for those with COPD. Multivariable Cox regression analyses showed that the only predictor of survival after commencing LTOT was the principal respiratory diagnosis. This study found that subjects prescribed LTOT had poor transplant-free survival after initiation, which was significantly worse for those with ILD compared to those with COPD. Despite their poor overall survival, worse than many cancers, only a minority were referred for palliative care input. Referrals to pulmonary rehabilitation were also suboptimal. This patient population had complex care needs requiring multidisciplinary management. Appropriate and early referrals to palliative care and improved care coordination for this complex group of patients are key areas for improvement in clinical practice.

Acute Exacerbation of Rheumatoid Arthritis Misdiagnosed as COVID-19: A Case Report

BackgroundRheumatoid arthritis (RA) is a systemic inflammatory connective tissue disease that affects 1–2% of the population worldwide. Pulmonary manifestations including interstitial lung disease (ILD), airway disease, pleural and vascular disease can be seen in up to 30–40% of patients with RA, which are recognized as the second most frequent cause of death in RA patients. The simultaneous occurrence of COVID-19 in RA patients with or without ILD, and the similarities and differences between RA-related ILD and COVID-19 lung findings have been reported in the literature. However, there was no reported case on differentiation of clinical findings of a patient with RA exacerbation causing a new diagnosis of ILD during the pandemic conditions.Case PresentationHere, we presented a patient with RA who was misdiagnosed as COVID-19 twice due to non-specific respiratory symptoms and ground-glass opacities observed in high-resolution CT. The misdiagnosis led to a delayed diagnosis of ILD and prolonged pulmonary symptoms.DiscussionClinicians must critically review patients throughout the diagnostic workup by thinking other diseases besides COVID-19, particularly in the absence of a confirmatory result. The link between ILD or ILD exacerbation and COVID-19 remains to be determined. While research continues in the field, it is important to consider the importance of COVID-19 in cases of ILD exacerbation, and vice versa.ConclusionDistinguishing lung imaging findings of COVID-19 from ILD is a major concern. Even though the primary manifestation of COVID-19 consists of respiratory symptoms, clinicians should be vigilant for other common conditions having the same symptoms. Clinicians should carefully distinguish a differential diagnosis between COVID-19 and a flare of rheumatic disease.

Interstitial lung disease in patients treated with Cyclin-Dependent Kinase 4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials.

BackgroundCyclin-Dependent Kinase (CDK) 4/6 inhibitors have shown significant clinical activity in cancer patients. However, some concerns regarding rare adverse events (AEs) have occurred including interstitial lung disease (ILD)/pneumonitis, for which data are deficient. The aim of this study was to evaluate the overall incidence and risk of ILD/pneumonitis related to CDK4/6 inhibitors in randomized controlled trials (RCTs).MethodsElectronic databases and ClinicalTrials.gov were searched from inception to October 1, 2021 for RCTs reporting the occurrence of LD/pneumonitis in cancer patients treated with CDK4/6 inhibitors. Peto odds ratios (Peto ORs) and 95% confidence intervals (CIs) were used to pool the study.Results12 RCTs with a total of 16,060 patients were eligible. The overall incidence of all-grade ILD/pneumonitis was 1.6% (131/8407) in the treatment group compared with 0.7% (50/7349) in the control group. CDK4/6 inhibitors significantly increased the risk of all-grade ILD/pneumonitis with a pooled Peto OR of 2.12 (95% CI [1.57, 2.86], P < 0.00001) with no heterogeneity (I2 = 0%, χ2 P = 0.98). A higher incidence of grade 3 or higher ILD/pneumonitis was also observed in the treatment group (0.2%, 16/7087) compared with the control group (0.05%, 3/6617) with a Peto OR of 3.22 (95% CI [1.28, 8.09], P = 0.01) with no heterogeneity (I2 = 0%, χ2 P = 0.62). Two grade 5 pneumonitis were reported in the included studies. Subgroup analyses did not show any significant difference.ConclusionsThe risk of all-grade and grade 3 or higher ILD/pneumonitis was higher in patients treated with CDK4/6 inhibitors compared to controls. The awareness for these rare AEs in the application of CDK4/6 inhibitors should be enhanced. Further studies are required to validate the mechanisms and the risk factors of ILD/pneumonitis with CDK4/6 inhibitors.

Concordance between myositis autoantibodies and anti-nuclear antibody patterns in a real-world, Australian cohort.

Myositis autoantibodies (MAs) were traditionally used as a diagnostic biomarker for idiopathic inflammatory myopathy (IIM). Its clinical utility had recently expanded to include interstitial lung disease (ILD) diagnosis. Depending on the patient cohort, MAs false positives can be common. Correlation between ANA indirect immunofluorescent (IIF) pattern and MAs may improve its positive predictive value (PPV). The aim of our study was to determine the PPV of MAs in IIM and ILD in a real-world patient cohort. We also assessed whether concordance between MAs and ANA IIF pattern can improve the PPV of positive MA results. Patients with positive MAs and corresponding ANA IIF pattern were identified from Sutherland Centre of Immunology, New South Wales Health Pathology, Australia. The corresponding health records were reviewed to identify each patient's primary diagnosis. χ2 test was used to compare the PPV between MA-ANA concordant and discordant groups. Between January 2016 and July 2019, 118 patients were positive for at least one MA (mean age 66.7 years, 55% female). The most frequently detected autoantibodies were Ro52, anti-synthetase antibodies and PM-Scl. The PPV of MAs for IIM or ILD was 47.4%. The overall concordance rate of MAs and ANA IIF pattern was 70.2%. Patients with concordant MA-ANA results were more likely to have true clinical disease (64.1% vs 17.8%, P<0.001). Myositis autoantibodies have a low PPV for IIM and ILD in a real-world patient cohort. A positive concordance with ANA IIF pattern can improve MA test accuracy.

Serum rheumatoid factor IgA, anti-citrullinated peptide antibodies with secretory components, and anti-carbamylated protein antibodies associate with interstitial lung disease in rheumatoid arthritis

ObjectiveRheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD.MethodsSera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay.ResultsThe comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively, P = 1.13 × 10− 8), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P = 1.00 × 10− 7). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively, P = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml, P = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively, P = 1.04X10− 11).ConclusionRF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.

Chronic Respiratory Diseases: Treatment and Prevention

The article investigates the therapeutic and preventive aspects of chronic respiratory diseases. The authors note that chronic respiratory diseases are among the most common non-communicable diseases worldwide, mainly due to the widespread distribution of harmful environmental, occupational and behavioral inhalation effects. In addition to chronic obstructive pulmonary disease (COPD) and asthma, chronic respiratory diseases include interstitial lung disease, pulmonary sarcoidosis, and pneumoconioses such as silicosis and asbestos. Unfortunately, chronic respiratory diseases have received proportionally less public attention and less research funding than other diseases such as cardiovascular diseases, cancer, stroke, diabetes and Alzheimer’s disease. Therefore, in order to better inform about the prevention, screening, treatment and research on chronic respiratory diseases, it is extremely important to understand their prevalence, morbidity and mortality both globally and regionally