2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis In Vivo Using Endobronchial Optical Coherence Tomography.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) affects subpleural lung, but is considered to spare small airways. Micro-CT studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. We use EB-OCT to evaluate small airways in early IPF and control subjects in vivo. METHODS: EB-OCT was performed in 12 IPF and 5 control subjects (matched by age, sex, smoking-history, height, BMI). IPF subjects had early disease with mild restriction (FVC: 83.5% predicted), diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for UIP present) and less affected (some but not all criteria for UIP present) sites. Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. RESULTS: Compared to control subjects (mean: 11.2 bronchioles/cm3; SD: 6.2), there was significant bronchiole reduction in IPF subjects (42% loss; mean: 6.5/cm3; SD: 3.4; p=0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; p<0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; p=0.024) sites. Stereology metrics showed IPF affected small airways were significantly larger and more distorted/irregular than in IPF less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (p=0.36-1.0). CONCLUSION: EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30 and 50%), even in areas minimally affected by disease, compared to matched controls. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

A Tai Chi Class Collaboratively Developed for Persons With Interstitial and Other Lung Diseases: An Ethnographic Investigation.

Background: Participating in physical activity (PA) can be challenging for persons with chronic and significant lung disease due to the multifaceted disruptive effects of their symptoms and variable disease course. Objectives: Our study investigates a novel approach to increasing PA by collaboratively and adaptively developing a Tai Chi (TC) class for and by persons with lung diseases and explores participants' perceptions of their experiences in the co-developed TC class. Methods: We initiated a collaboration between the Interstitial Lung Disease (ILD) Collaborative and the Tai Chi Foundation to develop a TC class appropriate for persons with ILD and other lung diseases. The TC class was offered online, during the early phases of the COVID-19 pandemic, when pulmonary patients were isolated socially. TC class sessions were held twice weekly for 12 weeks with 12 participants. Ethnographic field methods were used to collect observations and conduct interviews with teachers and students. The Social Ecological Model (SEM) for understanding factors in intrapersonal, interpersonal, social, and organizational contexts was used to explore ways in which wellness practices, particularly those involving changes in health behaviors, can be collaboratively conceived, and developed by persons with the lived experience of illness and community organizations that are sensitive to their personal and social contexts. The constant comparative method was used for data analysis. Results: Our findings include the importance of (1) creating a supportive class environment, characterized by interactive and reciprocal relationships among students and teachers; (2) alternating segments of movement and meditation to avoid fatigue and breathlessness; (3) cultivating sensory awareness and body trust, resting when needed and rejoining the movements when ready; (4) increasing the capacity to meditate through deepening presence and renewing the vital connection with inner and outer sources of energy; (5) reducing, through meditative movement, the persistent anxiety, isolation, and sense of loss that accompany chronic disease diagnosis and progression. Conclusion: We documented a collaboration between the TC and pulmonary communities to design a TC class for persons with chronic and significant lung disease. We employed the SEM to provide insights into how teachers, informed by their students, can use effective pedagogical skills to create core curricula with modifications appropriate for a specific population.

Diagnosis and Management of Myositis-Associated Lung Disease.

Although interstitial lung disease (ILD) is a leading cause of morbidity and mortality in patients with inflammatory myopathies, the current definition and diagnostic criteria of autoimmune myositis remain inadequate to capture the large proportion of patients with lung-dominant disease. As a result, these patients present unique diagnostic and treatment challenges for even the most experienced clinicians. This article highlights the emerging role of autoantibodies in the diagnosis, classification, and management of patients with ILD. We propose alternative nomenclature to facilitate research on this unique patient population. Additionally, evidence supporting the various therapies used in the treatment of myositis-associated ILD is reviewed. The classification and treatment of patients with myositis-associated ILD remains challenging. A standardized therapeutic approach to these patients is lacking, and prospective studies in the field are needed to determine optimal treatment regimens.

Diagnosis and Treatment of Lung Cancer in the Setting of Interstitial Lung Disease.

Interstitial lung disease (ILD) including idiopathic pulmonary fibrosis increases the risk of developing lung cancer. Diagnosing and staging lung cancer in patients with ILD is challenging and requires careful interpretation of computed tomography (CT) and fluorodeoxyglucose PET/CT to distinguish nodules from areas of fibrosis. Minimally invasive tissue sampling is preferred but may be technically challenging given tumor location, coexistent fibrosis, and pneumothorax risk. Current treatment options include surgery, radiation therapy, percutaneous thermal ablation, and systemic therapy; however, ILD increases the risks associated with each treatment option, especially acute ILD exacerbation.

Pulmonary amyloidosis as the presenting finding in a patient with multiple myeloma.

We present the case of a 58-year-old man who presented with dyspnea, cough, and weight loss and was ultimately diagnosed with pulmonary amyloidosis and multiple myeloma. Diagnosis was achieved with a lung biopsy which showed AL amyloid deposits involving the interstitium, vessels, and airway. He was treated with cyclophosphamide, bortezomib, and dexamethasone but died prior to completing treatment. His case is unique for the amyloid deposition found in all three lung compartments with clear pathophysiologic manifestations of each compartment, and the rapid disease progression that led to respiratory failure and death.

Myositis-associated interstitial lung disease: a comprehensive approach to diagnosis and management.

Interstitial lung disease (ILD) frequently complicates the inflammatory myopathies and at times is the most prominent clinical feature. Over the years, there has been a growing recognition for the strong association between seropositivity of several myositis-specific antibodies (MSAs) and lung involvement. Growing literature suggests that individual MSAs may influence the risk of developing ILD and are associated with pulmonary disease severity and various clinical sub-phenotypes. The presence of ILD in patients with myositis correlates with increased morbidity and mortality. As such, it presents a unique treatment challenge for both the rheumatology and pulmonary communities and requires a multidisciplinary approach to management. This review will discuss the role of serologies and invasive and non-invasive testing modalities utilised to diagnose and monitor patients with myositis-ILD. Current studies pertaining to the wide array of immunomodulatory therapies utilised in cases of progressive disease are also highlighted in detail.

Pulmonary histopathology of interstitial lung disease associated with antisynthetase antibodies.

BACKGROUND: We aimed to determine if antibody type is an indicator of pulmonary histopathology, using antisynthetase antibody positive interstitial lung disease (ILD) cases with lung biopsy or autopsy findings. METHODS: We conducted a comprehensive review of the English language literature in PubMed to identify ILD histopathology results for cases with antibodies against anti-aminoacyl-transfer RNA (tRNA) synthetases (anti-ARS antibodies), including Jo1, PL-12, PL-7, KS, ES, and OJ. We additionally identified patients who had ILD, anti-ARS antibodies, and a lung biopsy between 2015 and 2020 at Beth Israel Deaconess Medical Center. For each case, we documented the specific anti-ARS antibody and major histopathologic patterns identified on biopsy or autopsy, including usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), and acute lung injury (ALI). To determine if histopathology varied by antibody type, we compared the proportion of each of four major patterns by antibody type using the Fisher's Exact test. RESULTS: We identified 310 cases with pathology findings and anti-ARS antibody positivity, including 12 cases from our institution. The proportion of NSIP differed significantly across antibody type, found in 31% of Jo1 (p < 0.01), 67% of EJ (p < 0.01), and 63% of KS (p < 0.01) cases. OP was common in Jo1 (23%, p = 0.07), but rare in EJ (4%, p = 0.04) and KS (4%, p = 0.04). UIP was common in PL-12 alone (36%, p = 0.03). CONCLUSION: The frequency of histopathologic findings in ILD with anti-ARS positivity varies significantly by antibody type, and NSIP occurs in less than half of all cases.

A Case Report of Steroid-Resistant Cryptogenic Organizing Pneumonia Managed with Intravenous Immunoglobulins.

Fewer than ten reported cases of cryptogenic organizing pneumonia (COP) have been managed with intravenous immunoglobulins (IVIg). We report a case of a 72-year-old man who presented with a worsening cough and diffuse opacities on chest radiograph. Following no improvement with antibiotics and negative complementary investigations for infectious, malignant, and autoimmune etiologies, COP was confirmed on lung biopsy. Due to continued clinical deterioration despite high-dose steroids and new severe steroid-induced hallucinations, the patient was placed on intravenous immunoglobulins (IVIg) and mycophenolate mofetil and made a satisfactory recovery. IVIg should be considered as an important steroid-sparing alternative in patients with COP.

Antifibrotic Therapy: Is There a Role in Myositis-Interstitial Lung Disease?

Interstitial lung disease (ILD) is a cause of substantial morbidity and mortality amongst autoimmune diseases, including myositis. Despite first-line therapy with immunosuppression, many inflammatory ILDs advance to a fibrotic stage. In such patients, progressive fibrosis may be amenable to treatment with antifibrotic medications, which were initially studied and approved for the treatment of idiopathic pulmonary fibrosis. We here review the available data that support the use of antifibrotics in connective tissue diseases and progressive fibrosing ILDs. There is now a growing body of evidence in both large randomized clinical trials and on the evolving pathophysiologic pathways to support the use of antifibrotics in select patients with autoimmune ILD and a fibrotic phenotype. Further study of antifibrotics in combination with immunosuppressive medications, and in the myositis-ILD population, is needed.

Delphi Consensus Recommendations on Management of Dosing, Adverse Events, and Comorbidities in the Treatment of Idiopathic Pulmonary Fibrosis with Nintedanib.

PURPOSE: Nintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF), which slows disease progression. Management of patients with IPF receiving nintedanib can be complicated by tolerability issues, comorbidities, and concomitant medications. We developed consensus recommendations on the management of dosing, adverse events and comorbidities in patients with IPF treated with nintedanib. METHODS: A modified Delphi process using 3 questionnaires was used to survey 14 pulmonologists experienced in using nintedanib. Panelists rated their agreement with statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). Consensus was predefined as a mean score of ⩽-2.5 or ⩾+2.5 with a standard deviation not crossing zero. RESULTS: The panelists' recommendations were largely aligned with clinical trial data, real-world evidence, and the prescribing information, and provided additional guidance regarding minimizing gastrointestinal effects, periodic monitoring for liver dysfunction, caution with respect to concomitant administration of cytochrome P450 3A4 and P-glycoprotein 1 inhibitors and inducers and anticoagulants, and management of comorbidities. The panelists unanimously agreed that adverse event management should be individualized, based on careful consideration of the risks and benefits of each possible intervention and discussion with the patient. CONCLUSIONS: These consensus recommendations provide additional guidance on the appropriate management of IPF with nintedanib, for use alongside evidence-based literature and the prescribing information.

Vascular Pruning on CT and Interstitial Lung Abnormalities in the Framingham Heart Study.

BACKGROUND: Pulmonary vascular disease is associated with poor outcomes in individuals affected by interstitial lung disease. The pulmonary vessels can be quantified with noninvasive imaging, but whether radiographic indicators of vasculopathy are associated with early interstitial changes is not known. RESEARCH QUESTION: Are pulmonary vascular volumes, quantified from CT scans, associated with interstitial lung abnormalities (ILA) in a community-based sample with a low burden of lung disease? STUDY DESIGN AND METHODS: In 2,386 participants of the Framingham Heart Study, we used CT imaging to calculate pulmonary vascular volumes, including the small vessel fraction (a surrogate of vascular pruning). We constructed multivariable logistic regression models to investigate associations of vascular volumes with ILA, progression of ILA, and restrictive pattern on spirometry. In secondary analyses, we additionally adjusted for diffusing capacity and emphysema, and performed a sensitivity analysis restricted to participants with normal FVC and diffusing capacity. RESULTS: In adjusted models, we found that lower pulmonary vascular volumes on CT were associated with greater odds of ILA, antecedent ILA progression, and restrictive pattern on spirometry. For example, each SD lower small vessel fraction was associated with 1.81-fold greater odds of ILA (95% CI, 1.41-2.31; P < .0001), and 1.63-fold greater odds of restriction on spirometry (95% CI, 1.18-2.24; P = .003). Similar patterns were seen after adjustment for diffusing capacity for carbon monoxide, emphysema, and among participants with normal lung function. INTERPRETATION: In this cohort of community-dwelling adults not selected on the basis of lung disease, more severe vascular pruning on CT was associated with greater odds of ILA, ILA progression, and restrictive pattern on spirometry. Pruning on CT may be an indicator of early pulmonary vasculopathy associated with interstitial lung disease.

Controlled Delivery of 80 mg Aerosol Furosemide Does Not Achieve Consistent Dyspnea Relief in Patients.

PURPOSE: Aerosol furosemide may be an option to treat refractory dyspnea, though doses, methods of delivery, and outcomes have been variable. We hypothesized that controlled delivery of high dose aerosol furosemide would reduce variability of dyspnea relief in patients with underlying pulmonary disease. METHODS: Seventeen patients with chronic exertional dyspnea were recruited. Patients rated recently recalled breathing discomfort on a numerical rating scale (NRS) and the multidimensional dyspnea profile (MDP). They then performed graded exercise using an arm-ergometer. The NRS was completed following each exercise grade, and the MDP was repeated after a pre-defined dyspnea threshold was reached. During separate visits, patients received either aerosol saline or 80 mg of aerosol furosemide in a randomized, double-blind, crossover design. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the NRS and MDP. Treatment effect was defined as the difference between pre- and post-treatment NRS at end exercise, expressed in absolute terms as % Full Scale. "Responders" were defined as those showing treatment effect ≥ 20% of full scale. RESULTS: Final analysis included 15 patients. Neither treatment produced a statistically significant change in NRS and there was no significant difference between treatments (p = 0.45). There were four "responders" and one patient whose dyspnea worsened with furosemide; two patients were responders with saline, of whom one also responded to furosemide. No adverse events were reported. CONCLUSIONS: High dose controlled delivery aerosol furosemide was not statistically different from saline placebo at reducing exercise-induced dyspnea. However, a clinically meaningful improvement was noted in some patients.