Digital Lung Auscultation: Will Early Diagnosis of Fibrotic Interstitial Lung Disease Become a Reality?

Richeldi, Luca; Cottin, Vincent; Würtemberger, Gebhard; Kreuter, Michael; Calvello, Mariarosaria; Sgalla, Giacomo

doi:10.1164/rccm.201902-0306le

Cited by 11 publications

(14 citation statements)

References 15 publications

(14 reference statements)

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“…Currently, there are no effective therapies capable of targeting these underlying fibrotic changes in the lung, despite efforts directed toward developing antifibrotic therapies and many clinical trials . There is a pressing need to develop noninvasive imaging methodologies to enable early detection of fibrosis, longitudinally quantify lung fibrosis for staging during progression and regression upon treatment, facilitate patient selection for precision medicine, and improve preclinical drug discovery. , …”

Section: Discussionmentioning

confidence: 99%

“…To overcome limitations of linear chelators such as DTPA used in EP3533, including low in vivo metal stability and association with Gd 3+ retention in the bone, and constraints of translational applications, an oxyamine-functionalized derivative of Gd-DOTA has been developed to target allysine in oxidized collagen. , Caravan also reported an aldehyde-binding MRI probe Gd-Chyd to target lung fibrogenesis and an allysine-binding PET probe 68 Ga-NODAGA indole . A DOTA-based collagen targeted PET contrast agent was recently evaluated with rodents and IPF patients; ,, however, a histological validation to understand its target specificity has yet to be demonstrated. While Gadofosveset (Ablavar), an FDA-approved, gadolinium-based, albumin-binding contrast agent, has detected albumin extravasation in subjects with pulmonary fibrosis with tissue injury by MRI, it is not clear whether some component of these findings could be explained by very early fibrotic changes or neovascularization …”

Section: Discussionmentioning

confidence: 99%

“…Various efforts using single photon emission computed tomography (SPECT) or positron emission tomography (PET) for the detection of rodents and IPF patients have also been reported to address this currently unmet imaging need, ,,,, including an allysine-binding PET probe 68 Ga-NODAGA indole, and a DOTA-based collagen-targeted PET contrast agent that was recently evaluated with rodents and IPF patients. , Our developed collagen-targeted MRI contrast agent exhibits several major advantages over PET agents and CT, including: (i) higher tempo-spatial resolution during disease progression and regression in treatment from frequent longitudinal imaging and quantification of collagen expression levels without radiation exposure; (ii) reduced safety concerns with more accessibility to patient populations, including children and pregnant women; and (iii) broader application due to greater accessibility of MRI and lower demand for instrumentation, maintenance, and personal costs.…”

Section: Discussionmentioning

confidence: 99%

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Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent

Ibhagui

Han

et al. 2023

Chemical & Biomedical Imaging

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Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.collagen) to specifically bind to collagen I overexpressed in multiple lung diseases. When compared to clinically approved Gd3+ contrast agents, hProCA32.collagen exhibits significantly better r 1 and r 2 relaxivity values, strong metal binding affinity and selectivity, and transmetalation resistance. Here, we report the robust detection of early and late-stage lung fibrosis with stage-dependent MRI signal-to-noise ratio (SNR) increase, with good sensitivity and specificity, using a progressive bleomycin-induced IPF mouse model. Spatial heterogeneous mapping of usual interstitial pneumonia (UIP) patterns with key features closely mimicking human IPF, including cystic clustering, honeycombing, and traction bronchiectasis, were noninvasively detected by multiple MR imaging techniques and verified by histological correlation. We further report the detection of fibrosis in the lung airway of an electronic cigarette-induced COPD mouse model, using hProCA32.collagen-enabled precision MRI (pMRI), and validated by histological analysis. The developed hProCA32.collagen is expected to have strong translational potential for the noninvasive detection and staging of lung diseases, and facilitating effective treatment to halt further chronic lung disease progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent

Ibhagui

Han

et al. 2023

Chemical & Biomedical Imaging

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“…Quantitative digital analysis of lung sounds could be useful for early diagnosis and to intercept the progression of the disease [7,8].…”

Section: Introductionmentioning

confidence: 99%

Possible Role of Chest Ultrasonography for the Evaluation of Peripheral Fibrotic Pulmonary Changes in Patients Affected by Idiopathic Pulmonary Fibrosis—Pilot Case Series

et al. 2020

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Lung ultrasonography (LUS) provides an estimation of peripheral airspace (PAS) geometry of the lung. Altered PAS produces sonographic interstitial syndrome (SIS). Idiopathic pulmonary fibrosis (IPF) involves peripheral lung with altered PAS. The aim of the study is to correlate echographic patterns with peripheral fibrotic changes on high-resolution Chest CT scan (HRCT). Patients underwent LUS and HRCT on the same date. Four LUS patterns were described: (1) near normal; (2) SIS with predominance of reverberant artifacts; (3) SIS with vertical predominance; (4) white lung. Four HRCT grades of peripheral fibrotic infiltrates were reported: grade 1 mild; grade 2 moderate; grade 3 severe; grade 4 massive or honeycomb. LUS pattern 1 was indicative of mild to moderate fibrotic alterations in 100% of cases. LUS pattern 2 matched with HRCT grade 2 in 24 out of 30 cases (77%). Huge discordance in four cases because of large honeycomb cysts. LUS pattern 3 was indicative of severe to massive alterations in 100% of cases. LUS pattern 4 showed a heterogeneous distribution of HRCT grades, severe changes, and ground glass opacities (GGO). This preliminary work demonstrates some level of agreement between LUS patterns and HRCT grades. Limitations and methodological issues have been shown to support subsequent studies of agreement.

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“…In an ongoing, multi-center clinical trial (clinicaltrials.gov identifier: NCT03503188), digital lung sounds and basic patient characteristics are being prospectively collected from patients with IPF and from symptom-matched control subjects. A well-established teaching device for lung sounds will be used as a reference [ 55 ].…”

Section: Role Of Technology In Respiratory Medicinementioning

confidence: 99%

The Current and Future Role of Technology in Respiratory Care

2022

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Over the past few decades, technology and improvements in artificial intelligence have dramatically changed major sectors of our day-to-day lives, including the field of healthcare. E-health includes a wide range of subdomains, such as wearables, smart-inhalers, portable electronic spirometers, digital stethoscopes, and clinical decision support systems. E-health has been consistently shown to enhance the quality of care, improve adherence to therapy, and allow early detection of worsening in chronic pulmonary diseases. The present review addresses the current and potential future role of major e-health tools and approaches in respiratory medicine, with the aim of providing readers with trustful and updated evidence to increase their awareness of the topic, and to allow them to optimally benefit from the latest innovation technology. Collected literature evidence shows that the potential of technology tools in respiratory medicine mainly relies on three fundamental interactions: between clinicians, between clinician and patient, and between patient and health technology. However, it would be desirable to establish widely agreed and adopted standards for conducting trials and reporting results in this area, as well as to take into proper consideration potentially relevant pitfalls related to privacy protection and compliance with regulatory procedures.

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Digital Lung Auscultation: Will Early Diagnosis of Fibrotic Interstitial Lung Disease Become a Reality?

Cited by 11 publications

References 15 publications

Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent

Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent

Possible Role of Chest Ultrasonography for the Evaluation of Peripheral Fibrotic Pulmonary Changes in Patients Affected by Idiopathic Pulmonary Fibrosis—Pilot Case Series

The Current and Future Role of Technology in Respiratory Care

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