Treatment approach to connective tissue disease-associated interstitial lung disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Wilson TM
PROVIDER: S-EPMC9308694 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Publications
Treatment approach to connective tissue disease-associated interstitial lung disease.
Wilson Timothy M TM Solomon Joshua J JJ Demoruelle M Kristen MK
Current opinion in pharmacology 20220601
Interstitial lung disease (ILD) is a common manifestation in connective tissue diseases (CTD), such as rheumatoid arthritis (RA), systemic sclerosis (SSc), and inflammatory myositis (IM). ILD is associated with significant morbidity and mortality in nearly all CTD highlighting the critical need for effective treatment strategies in this patient population. In this review, we will summarize the approach to treatment when there is concern for CTD-ILD and highlight recent advancements in therapeuti ...[more]
Similar Datasets
Project description:Interstitial lung disease (ILD) is one of the most serious pulmonary complications associated with connective tissue diseases (CTDs), resulting in significant morbidity and mortality. Although the various CTDs associated with ILD often are considered together because of their shared autoimmune nature, there are substantial differences in the clinical presentations and management of ILD in each specific CTD. This heterogeneity and the cross-disciplinary nature of care have complicated the conduct of prospective multicenter treatment trials and hindered our understanding of the development of ILD in patients with CTD. In this update, we present new information regarding the diagnosis and treatment of patients with ILD secondary to systemic sclerosis, rheumatoid arthritis, dermatomyositis and polymyositis, and Sjögren syndrome. We review information on risk factors for the development of ILD in the setting of CTD. Diagnostic criteria for CTD are presented as well as elements of the clinical evaluation that increase suspicion for CTD-ILD. We review the use of medications in the treatment of CTD-ILD. Although a large, randomized study has examined the impact of immunosuppressive therapy for ILD secondary to systemic sclerosis, additional studies are needed to determine optimal treatment strategies for each distinct form of CTD-ILD. Finally, we review new information regarding the subgroup of patients with ILD who meet some, but not all, diagnostic criteria for a CTD. A careful and systematic approach to diagnosis in patients with ILD may reveal an unrecognized CTD or evidence of autoimmunity in those previously believed to have idiopathic ILD.
| S-EPMC3590889 | biostudies-other
Project description:BACKGROUND:Spontaneous pneumothorax is a complication that occurs in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD); however, few studies on the clinical implications of pneumothorax for patients with CTD-ILD have been performed. OBJECTIVES:This study aimed to investigate the incidence and prognostic significance of pneumothorax and the risk factors for its onset in patients with CTD-ILD. METHODS:This study included 140 consecutive patients with CTD-ILD. Clinical characteristics, laboratory findings, pulmonary function test results, and chest high-resolution computed tomography (HRCT) images were retrospectively evaluated. RESULTS:A total of 18 patients (12.9%) developed pneumothorax during their clinical course. The cumulative incidence of pneumothorax from the time of CTD-ILD diagnosis was 6.5%, 8.7%, and 11.3% at 1, 3, and 5 years, respectively. The 10-year survival rate was significantly lower in patients with pneumothorax (29.6%) than that in those without pneumothorax (81.3%). The development of pneumothorax was significantly associated with poor prognosis (HR 22.0; p < 0.010). Furthermore, a lower body mass index, greater extent of reticular abnormalities on HRCT, and administration of methylprednisolone pulse therapy were significantly associated with the development of pneumothorax. CONCLUSION:Pneumothorax is a serious complication in the clinical course of patients with CTD-ILD and the onset of pneumothorax predicts a poor outcome.
| S-EPMC7340294 | biostudies-literature
Project description:The lung is a common site of complications of systemic connective tissue disease (CTD), and lung involvement can present in several ways. Interstitial lung disease (ILD) and pulmonary hypertension are the most common lung manifestations in CTD. Although it is generally thought that interstitial lung disease develops later on in CTD it is often the initial presentation ("lung dominant" CTD). ILD can be present in most types of CTD, including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, polymyositis or dermatomyositis, Sjögren's syndrome, and mixed connective tissue disease. Despite similarities in clinical and pathologic presentation, the prognosis and treatment of CTD associated ILD (CTD-ILD) can differ greatly from that of other forms of ILD, such as idiopathic pulmonary fibrosis. Pulmonary hypertension (PH) can present as a primary vasculopathy in pulmonary arterial hypertension or in association with ILD (PH-ILD). Therefore, detailed history, physical examination, targeted serologic testing, and, occasionally, lung biopsy are needed to diagnose CTD-ILD, whereas both non-invasive and invasive assessments of pulmonary hemodynamics are needed to diagnose pulmonary hypertension. Immunosuppression is the mainstay of treatment for ILD, although data from randomized controlled trials (RCTs) to support specific treatments are lacking. Furthermore, treatment strategies vary according to the clinical situation-for example, the treatment of a patient newly diagnosed as having CTD-ILD differs from that of someone with an acute exacerbation of the disease. Immunosuppression is indicated only in select cases of pulmonary arterial hypertension related to CTD; more commonly, selective pulmonary vasodilators are used. For both diseases, comorbidities such as sleep disordered breathing, symptoms of dyspnea, and cough should be evaluated and treated. Lung transplantation should be considered in patients with advanced disease but is not always feasible because of other manifestations of CTD and comorbidities. Clinical trials of novel therapies including immunosuppressive therapies are needed to inform best treatment strategies.
| S-EPMC6887350 | biostudies-literature
Project description:Purpose of reviewThis review aims to collate current evidence on the screening, diagnosis, and treatment of various connective tissue disease (CTD)-associated interstitial lung diseases (CTD-ILD) and present a contemporary framework for the management of such patients. It also seeks to summarize treatment outcomes including efficacy and safety of immunosuppressants, anti-fibrotics, and stem cell transplantation in CTD-ILD.Recent findingsScreening for ILD has been augmented by the use of artificial intelligence, ultra-low dose computerized tomography (CT) of the chest, and the use of chest ultrasound. Serum biomarkers have not found their way into clinical practice as yet. Identifying patients who need treatment and choosing the appropriate therapy is important to minimize the risk of therapy-related toxicity. The first-line drugs for systemic sclerosis (SSc) ILD include mycophenolate and cyclophosphamide. Nintedanib, an anti-fibrotic tyrosine kinase inhibitor, is approved for use in SSc-ILD. The US Food and Drug Administration (FDA) has recently approved tocilizumab subcutaneous injection for slowing the rate of decline in pulmonary function in adult patients with SSc-ILD. Autologous stem cell transplantation may have a role in select cases of SSc-ILD.SummaryCTD-ILD is a challenging area with diverse entities and variable outcomes. High-resolution CT is the investigative modality of choice. Treatment decisions need to be individualized and are based on patient symptoms, lung function, radiologic abnormalities, and the risk of disease progression. Precision medicine may play an important role in determining the optimal therapy for an individual patient in the future.
| S-EPMC9062859 | biostudies-literature
Project description:Background: Interstitial lung disease (ILD) is a common pulmonary disease often associated with significant morbidity and mortality in patients with connective tissue diseases (CTD). Currently, no gold-standard therapies are available for CTD-ILD. Recently, several studies have proposed that rituximab (RTX) may be effective for the treatment of CTD-ILD. Objectives: This study aimed to systematically evaluate the efficacy and safety of RTX for the treatment of CTD-ILD. Methods: Studies were selected from PubMed, Embase, and Cochrane Library, up to 20 July 2022. Improvement and stable rates were extracted as the main outcomes and pooled using the weighted mean proportion with fixed or random-effects models, in case of significant heterogeneity (I 2 > 50%). Safety analysis was performed based on the adverse events reported in all of the studies. Results: Thirteen studies (312 patients) were included in the meta-analysis. The follow-up durations ranged from 6 to 36 months. The pooled improvement rate was 35.0% (95% CI: 0.277-0.442), while the pooled stable rate was 59.2% (95% CI: 0.534-0.656). Anti-synthetase syndrome associated with ILD [ASS-ILD, 48.1% (95% CI, 0.373-0.620)] and idiopathic inflammatory myopathies associated with ILD [IIM-ILD, non-ASS, 47.4% (95% CI, 0.266-0.846)] had higher improvement rates than the other types. A total of 106 adverse events associated with RTX or progressive ILD were reported among the 318 patients, 55.7% of which were mild. Among 19 deaths, 17 were due to ILD progression, one to severe pulmonary arterial hypertension, and one to Pneumocystis jirovecii infection. Conclusion: RTX, which exhibits a satisfactory safety profile, is an effective treatment option for CTD-ILD, even in patients who fail to respond to other therapies. Further randomized trials are needed to assess the efficacy of rituximab compared to other treatments for CTD-ILD. Systematic review registration: PROSPERO, identifier (CRD42022363403).
| S-EPMC9650441 | biostudies-literature
Project description:ObjectivesInterstitial lung disease (ILD) in CTDs has highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality, and immunosuppression response.MethodsPatients with CTD-ILD had high-resolution chest CT (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern [usual interstitial pneumonia (UIP); non-specific interstitial pneumonia (NSIP); organizing pneumonia (OP); fibrotic hypersensitivity pneumonitis (fHP); and other]. Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed-effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment.ResultsAmong 645 CTD-ILD patients, the most frequent CTDs were SSc (n = 215), RA (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with the case for patients with UIP, FVC decline was slower in patients with NSIP (by 1.1%/year, 95% CI 0.2, 1.9) or OP (by 3.5%/year, 95% CI 2.0, 4.9), and mortality was lower in patients with NSIP [hazard ratio (HR) 0.65, 95% CI 0.45, 0.93] or OP (HR 0.18, 95% CI 0.05, 0.57), but higher in fHP (HR 1.58, 95% CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95% CI 1.4, 2.8), with no change for UIP or fHP.ConclusionMultiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.
| S-EPMC11443038 | biostudies-literature
Project description:BackgroundPirfenidone (PFD) is commonly applied for antifibrotic treatment in patients with idiopathic pulmonary fibrosis but has rarely been studied in cases with connective tissue disease-associated interstitial lung diseases (CTD-ILDs).ObjectivesWe aimed to examine the efficacy of PFD in patients with CTD-ILD based on real-world data.DesignA retrospective cohort study.MethodsThis study assessed the clinical features of CTD-ILD patients with or without a 6-month PFD treatment. A linear mixed effects model was employed to evaluate the effectiveness of PFD in alleviating lung function changes. Differences in response to PFD were analyzed based on CTD subtype, imaging classification, and pattern of pulmonary function at baseline.ResultsA total of 289 patients with CTD-ILD were included, with 155 (53.6%) receiving PFD treatment and the remaining constituting the control group. Patients with the usual interstitial pneumonia (UIP) pattern were more likely to receive PFD treatment, and a relatively lower proportion of cases in the PFD group received immunosuppressive therapies compared to the control group (p < 0.05). At the 6-month follow-up, patients in the PFD group demonstrated a more significant improvement in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) (ΔFVC%: 2.9% vs 0.45%, p = 0.009; ΔDLCO%: 1.9% vs -1.1%, p = 0.004). In the linear mixed model analysis, there was a statistically significant group-time interaction between FVC% and DLCO% changes over time (FVC%: β = 4.52, p < 0.001; DLCO%: β = 4.13, p = 0.003). Furthermore, subgroup analysis indicated that pirfenidone may have superior therapeutic effects in patients with systemic sclerosis (SSc)-associated ILD, non-UIP pattern, and restrictive pattern of lung function at baseline.ConclusionThis study provided real-world data demonstrating the effectiveness of PFD in terms of lung function improvement in patients with CTD-ILD.
| S-EPMC11544659 | biostudies-literature
Project description:Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease (CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different-yet largely unknown-mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population.
| S-EPMC7815631 | biostudies-literature
Project description:Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a severe manifestation of CTD that leads to significant morbidity and mortality. Clinically, ILD can occur in diverse CTDs. Pathologically, CTD-ILD is characterized by various histologic patterns, such as nonspecific interstitial pneumonia, organizing pneumonia, and usual interstitial pneumonia. Abnormal immune system responses have traditionally been instrumental in its pathophysiology, and various changes in immune cells have been described, especially in macrophages. This article first briefly overviews the epidemiology, clinical characteristics, impacts, and histopathologic changes associated with CTD-ILD. Next, it summarizes the roles of various signaling pathways in macrophages or products of macrophages in ILD, helped by insights gained from animal models. In the following sections, this review returns to studies of macrophages in CTD-ILD in humans for an overall picture of the current understanding. Finally, we direct attention to potential therapies targeting macrophages in CTD-ILD in investigation or in clinical trials, as well as the future directions regarding macrophages in the context of CTD-ILD. Although the field of macrophages in CTD-ILD is still in its infancy, several lines of evidence suggest the potential of this area.
| S-EPMC10419312 | biostudies-literature
Project description:Interstitial lung disease (ILD) represents a severe pulmonary complication of connective tissue diseases, rheumatoid arthritis (RA), and antineutrophil cytoplasmic antibody-associated vasculitis. Treatment of ILD, mainly based on immunosuppression, remains challenging. Rituximab (RTX), a monoclonal antibody binding to CD20, is considered a valuable therapeutic choice in cases of refractory ILD. Here, we review the available efficacy and safety data on the use of RTX in the treatment of rheumatic disease-related ILD. Despite controversial efficacy data, RTX seems to be able to stabilize or improve ILD related to RA and antisynthetase syndrome and in established and severe ILD complicating systemic sclerosis. Fewer data are available regarding ILD related to Sjögren syndrome, systemic lupus erythematosus, and antineutrophil cytoplasmic antibody-associated vasculitis. To date, few prospective studies are available and randomized trials are still ongoing with the purpose of exploring the role of RTX in this condition, including the supposed relationship between efficacy and ILD radiologic patterns and safety data, up to now derived mainly from RA studies. Despite an overall acceptable safety profile, concerns remain regarding an increased infectious disease risk in patients with ILD as well as possible lung toxicity and the increased rate of immune-mediated reactions in patients with connective tissue diseases. In conclusion, RTX is a relevant therapeutic option for rheumatic disease-related ILD despite the existing uncertainties; ongoing trials are expected to clarify its use.
| S-EPMC7813433 | biostudies-literature