Leveraging AI technology in sarcoidosis.

PURPOSE OF REVIEW: Sarcoidosis is a systemic, granulomatous disease of uncertain cause. Diagnosis may be difficult, prognosis uncertain and response to treatment unpredictable. The application of artificial intelligence to sarcoidosis may provide clinical decision support for these challenges. This review will provide an overview of current and potential future applications of artificial intelligence in sarcoidosis. RECENT FINDINGS: The predominant application of artificial intelligence in sarcoidosis is imaging. Imaging models may differentiate sarcoidosis from other pulmonary disorders. Models, which predict survival and identify key factors relevant to prognosis are also available. The application of cluster analysis to organize sarcoidosis patients into developmental phenotypes is underway. Machine learning algorithms to evaluate the treatment response of sarcoidosis patients do not yet exist but similar models may evaluate patients with other inflammatory disease. The potential applications of artificial intelligence to sarcoidosis is vast, but there are practical limitations that warrant consideration. These include: the accessibility of data, biases in data, cost and privacy. SUMMARY: The application of artificial intelligence in medicine is still in its early stages but models are poised to support the diagnostic and prognostic challenges in sarcoidosis patients. The predictive power of these artificial intelligence is likely to come from combining various models, trained on content-rich datasets from phenotypically heterogeneous sarcoidosis patients.

Current Applications of Artificial Intelligence in Sarcoidosis.

PURPOSE: Sarcoidosis is a complex disease which can affect nearly every organ system with manifestations ranging from asymptomatic imaging findings to sudden cardiac death. As such, diagnosis and prognostication are topics of continued investigation. Recent technological advancements have introduced multiple modalities of artificial intelligence (AI) to the study of sarcoidosis. Machine learning, deep learning, and radiomics have predominantly been used to study sarcoidosis. METHODS: Articles were collected by searching online databases using keywords such as sarcoid, machine learning, artificial intelligence, radiomics, and deep learning. Article titles and abstracts were reviewed for relevance by a single reviewer. Articles written in languages other than English were excluded. CONCLUSIONS: Machine learning may be used to help diagnose pulmonary sarcoidosis and prognosticate in cardiac sarcoidosis. Deep learning is most comprehensively studied for diagnosis of pulmonary sarcoidosis and has less frequently been applied to prognostication in cardiac sarcoidosis. Radiomics has primarily been used to differentiate sarcoidosis from malignancy. To date, the use of AI in sarcoidosis is limited by the rarity of this disease, leading to small, suboptimal training sets. Nevertheless, there are applications of AI that have been used to study other systemic diseases, which may be adapted for use in sarcoidosis. These applications include discovery of new disease phenotypes, discovery of biomarkers of disease onset and activity, and treatment optimization.

Utility of electrophysiologic testing for sudden death risk stratification in cardiac sarcoidosis patients with mildly impaired left ventricular function.

BACKGROUND: Ventricular arrhythmias (VA) account for at least 25% of deaths caused by cardiac sarcoidosis (CS) and may arise in patients with mildly impaired LVEF (>35%). OBJECTIVE: In the current study, we examine whether EP study may be used for sudden death risk stratification in CS patients who have mildly impaired LVEF and a diagnosis of highly probable or probable CS according to the World Association of Sarcoidosis and Other Granulomatous Diseases Sarcoidosis Organ Assessment Instrument (WASOGI). METHODS: All patients: (1) exhibited a diagnosis of highly probable or probable CS according to the WASOGI, (2) exhibited cardiac MRI findings consistent with CS, (3) exhibited LVEF >45% and (4) underwent EP study. Device interrogations, transmissions and medical records were reviewed for all patients. RESULTS: We identified 46 CS patients with mildly impaired LVEF. VA were induced in 11 patients and 10/11 patients underwent ICD placement. Thirty-five patients had no VA and 24/35 patients underwent placement of an ILR. During the follow-up period, the VA event rate was 6.5%. The negative and positive predictive values of the EP study for the development of VA were 100% and 27.2%, respectively. CONCLUSIONS: In CS patients with mildly impaired LVEF and a diagnosis of highly probable or probable CS, a negative EP study was highly predictive of the absence of VA. The successful execution of future prospective studies is contingent upon enrollment of phenotypically homogenous cardiac sarcoidosis patients.

Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool.

INTRODUCTION: A Case Control Etiology of Sarcoidosis Study (ACCESS) sarcoidosis organ assessment instrument has been used for more than a decade to establish uniform standards for the probability of sarcoidosis organ involvement. The ACCESS instrument has become increasingly outdated as new technologies have been developed. Furthermore, the ACCESS instrument failed to address all possible organs involved with sarcoidosis. For these reasons, the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) developed a new sarcoidosis organ assessment instrument. METHODS: Clinical sarcoidosis experts assessed various clinical manifestations for the probability of sarcoidosis organ involvement. Two criteria were required to apply this assessment: 1) histologic evidence of granulomatous inflammation of unknown cause in an organ that was not being assessed; 2) the clinical manifestation being addressed required that alternative causes other than sarcoidosis had been reasonably excluded. Clinical manifestations were assessed as either: a) highly probable: likelihood of sarcoidosis causing this manifestation of at least 90%.; b) probable: likelihood of sarcoidosis causing this manifestation of between 50 and 90%; c) possible: likelihood of sarcoidosis causing this manifestation of less than 50%. The sarcoidosis experts voted on the likelihood of sarcoidosis causing each manifestation using Delphi study methodology where at least 70% agreement of the experts was needed for consensus. RESULTS: Various clinical manifestations were classified as highly probable, at least probable, possible, or indeterminate when no consensus could be reached. CONCLUSION: An instrument was developed by expert opinion that may be useful for the clinician and researcher in establishing criteria for sarcoidosis organ involvement.

Sarcoidosis of the upper and lower airways.

Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed.

Recent advances in sarcoidosis.

Sarcoidosis, a systemic granulomatous disease of undetermined etiology, is characterized by a variable clinical presentation and course. During the past decade, advances have been made in the study of sarcoidosis. The multicenter ACCESS (A Case Control Etiologic Study of Sarcoidosis) trial recruited > 700 subjects with newly diagnosed sarcoidosis and matched control subjects. Investigators were unable to identify a single cause of sarcoidosis, but ACCESS paved the way for subsequent etiologic studies. The Mycobacterium tuberculosis catalase-peroxidase protein has been identified as a potential sarcoidosis antigen. Genetic aspects of the disease have been elucidated further. Genome-wide scans have identified candidate genes. Gene expression analyses have defined cytokine dysregulation in sarcoidosis more clearly. Although the criteria for diagnosis have not changed, sarcoidosis remains a diagnosis of exclusion best supported by a tissue biopsy specimen that demonstrates noncaseating granulomas in a patient with compatible clinical and radiologic features of the disease. Endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated diagnosis, often eliminating the need for more invasive procedures, such as mediastinoscopy. PET scanning has proven valuable in locating occult sites of active disease. Currently, no reliable prognostic biomarkers have been identified. The tumor necrosis factor inhibitors, a relatively new class of agents, have been used in patients with refractory disease. It is unclear whether phosphodiesterase-5 inhibitors, prostaglandin analogs, or endothelin antagonists should be used for the treatment of sarcoidosis-associated pulmonary hypertension.

Spectrum of fibrosing diffuse parenchymal lung disease.

The interstitial lung diseases are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the pulmonary interstitium. In 2002, the American Thoracic Society and the European Respiratory Society revised the classification of interstitial lung diseases and introduced the term diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are a subtype of diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are subdivided into usual interstitial pneumonia (with its clinical counterpart idiopathic interstitial pneumonia), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and lymphocytic pneumonia. Sarcoidosis and hypersensitivity pneumonitis are the 2 most common granulomatous diffuse parenchymal lung diseases. Rheumatoid arthritis, systemic sclerosis, and dermatomyositis/polymyositis (causing antisynthetase syndrome) are diffuse parenchymal lung diseases of known association because these conditions are associated with connective tissue disease. Hermansky-Pudlak syndrome is a rare genetic diffuse parenchymal lung disease characterized by the clinical triad of pulmonary disease, oculocutaneous albinism, and bleeding diathesis. This review provides an overview of the chronic fibrosing diffuse parenchymal lung diseases. Its primary objective is to illuminate the clinical challenges encountered by clinicians who manage the diffuse parenchymal lung diseases regularly and to offer potential solutions to those challenges. Treatment for the diffuse parenchymal lung diseases is limited, and for many patients with end-stage disease, lung transplantation remains the best option. Although much has been learned about the diffuse parenchymal lung diseases during the past decade, research in these diseases is urgently needed.

"End-stage" pulmonary fibrosis in sarcoidosis.

Pulmonary fibrosis is an unusual "end stage" in patients with sarcoidosis. Fibrosis occurs in a minority of patients, and presents with a unique physiologic combination of airways dysfunction (obstruction) superimposed on the more common restrictive dysfunction. Imagin techniques are essential to the diagnosis, assessment and treatment of pulmonary fibrosis. Standard chest radiographs and CT scans may reveal streaks, bullae, cephalad retraction of the hilar areas, deviation of the trachea and tented diaphragm. Positive gallium and PET scans indicate residual reversible granulomatous disease and are important guides to therapy decisions. Treatment, usually with corticosteroids, is effective in those patients with positive scans, but fibrosis does not improve with any treatment. With severe functional impariment and patient disability, pulmonary hypertension and right heart failure may supervene for which the patient will require treatment. Oxygen, careful diuresis, sildenafil and bosentan may be salutary. These patients are candidates for lung transplantation.