Publications by authors named "Gary Hunninghake"

This retrospective study developed an automated algorithm for 3D segmentation of adipose tissue and paravertebral muscle on chest CT using artificial intelligence (AI) and assessed its feasibility. The study included patients from the Boston Lung Cancer Study (2000-2011). For adipose tissue quantification, 77 patients were included, while 245 were used for muscle quantification.

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Objectives: To explore the association between the extent of CT abnormalities by quantitative imaging analysis (QIA) and clinical/physiological disease parameters in patients with antisynthetase syndrome associated interstitial lung disease (ARS-ILD).

Methods: We analysed 20 patients with antisynthetase antibodies and active ILD enrolled in the Abatacept in Myositis-Associated Interstitial Lung Disease study. High-resolution chest CT was obtained at weeks 0, 24 and 48 and QIA scored the extent of ground glass (quantitative score for ground glass), fibrosis (quantitative score for lung fibrosis, QLF) and total ILD (quantitative ILD, QILD).

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Rationale: Rheumatoid arthritis (RA) has been implicated in interstitial lung disease (ILD) as majority of studies have been comprised of patients with known RA. However, it remains unclear whether an underlying risk for RA in combination with genetic risk for pulmonary fibrosis is associated with radiological markers of early lung injury and fibrosis in broader population samples.

Objective: Determine whether genetic and serological biomarkers of RA risk in combination with the (rs35705950) risk allele (T) are associated with interstitial lung abnormalities (ILA) on computed tomography (CT) scans.

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Article Synopsis
  • Researchers are developing automated models using machine learning to predict interstitial lung abnormalities (ILAs) in CT scans, as current methods rely heavily on manual assessments, which can be less efficient.
  • The study analyzed 1,382 CT scans from the Boston Lung Cancer Study, with radiologists serving as a reference point to identify ILAs; the scans were categorized into three groups: ILA present, indeterminate, and no ILA.
  • Various machine learning classifiers were tested for accuracy, revealing that certain models performed better in identifying ILAs, highlighting the potential for automated methods to improve clinical decision-making in lung health.
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Objective: The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD).

Method: We analyzed data from the Abatacept in Myositis Associated Interstitial lung disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD.

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Article Synopsis
  • Individuals with interstitial lung abnormalities (ILA) may have suspected interstitial lung disease (ILD), which can lead to worse health outcomes and higher mortality rates.
  • A study of 9,588 participants found that 2.8% had prevalent ILD, with a 52% mortality rate after about 10.6 years, significantly higher than those with ILA only (33%).
  • Progression of ILD, particularly the presence of fibrosis and CT changes, was linked to increased mortality, emphasizing the need for careful monitoring of those with suspected ILD.
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Objective: Racial and ethnic differences in presentation and outcomes have been reported in systemic sclerosis (SSc) and SSc-interstitial lung disease (ILD). However, prior studies have limited diversity. We aim to evaluate if there are racial/ethnic differences associated with ILD, time intervals between SSc and ILD and with emergency department (ED) visit or hospitalization rates.

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  • High-resolution computed tomography (HRCT) is essential for diagnosing Idiopathic Pulmonary Fibrosis (IPF), but it can be confused with other interstitial lung diseases (ILDs) due to similar radiologic patterns.
  • Researchers used mass spectrometry to analyze plasma extracellular vesicles (EVs) from different patient groups, identifying a five-protein signature that distinguishes IPF from other ILDs and healthy individuals.
  • The study validated these biomarkers in independent cohorts, showing high accuracy but emphasizes the need for further large-scale studies to confirm their clinical application.
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Objective: To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators.

Methods: We analysed longitudinal data from two prospective cohorts: the UK Biobank and COPDGene. Spirometry was conducted at baseline and a second visit after 5-7 years.

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Interstitial lung abnormalities (ILAs) are incidental findings on computed tomography scans, characterized by nondependent abnormalities affecting more than 5% of any lung zone. They are associated with factors such as age, smoking, genetic variants, worsened clinical outcomes, and increased mortality. Risk stratification based on clinical and radiological features of ILAs is crucial in clinical practice, particularly for identifying cases at high risk of progression to pulmonary fibrosis.

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Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common SNPs. The promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF.

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Rationale: Racial and ethnic differences in presentation and outcomes have been reported in systemic sclerosis (SSc) and SSc-interstitial lung disease (ILD). However, diverse cohorts and additional modeling can improve understanding of risk features and outcomes, which is important for reducing associated disparities.

Objectives: To determine if there are racial/ethnic differences associated with SSc-ILD risk and age; time intervals between SSc and ILD, and with emergency department (ED) visit or hospitalization rates.

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Article Synopsis
  • - The study aimed to examine the incidence and severity of pulmonary embolism (PE) in COVID-19 patients during different variant periods (ancestral strain, Alpha, Delta, and Omicron) to see if newer variants and vaccinations reduced these factors.
  • - Researchers analyzed data from 720 COVID-19 patients who had a CT pulmonary angiogram within a specific timeframe, finding that PE diagnoses varied slightly across variant periods but not significantly.
  • - The results showed that the incidence and location of PE (in various artery types) did not significantly differ between the ancestral strain and the variants, suggesting that the risk remained consistent despite the presence of newer variants.
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Objectives: There have been limited investigations of the prevalence and mortality impact of quantitative computed tomography (QCT) parenchymal lung features in rheumatoid arthritis (RA). We examined the cross-sectional prevalence and mortality associations of QCT features, comparing RA and non-RA participants.

Methods: We identified participants with and without RA in COPDGene, a multicentre cohort study of current or former smokers.

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Article Synopsis
  • The study aimed to explore how common interstitial lung abnormalities (ILAs) are in individuals with rheumatoid arthritis (RA) compared to those without, and how these conditions affect mortality.
  • Researchers analyzed data from a cohort of current and former smokers, using chest scans to identify and classify ILAs while considering the impact of various lifestyle factors and genetics.
  • Results showed that RA patients had a significantly higher prevalence of ILAs (16.9%) compared to non-RA individuals (5.0%), with RA patients who had ILAs experiencing a threefold increase in all-cause mortality, highlighting the need for better screening and management.
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Introduction: Interstitial lung abnormalities (ILA) often represent early fibrotic changes that can portend a progressive fibrotic phenotype. In particular, the fibrotic subtype of ILA is associated with increased mortality and rapid decline in lung function. Understanding the differential gene expression that occurs in the lungs of participants with fibrotic ILA may provide insight into development of a useful biomarker for early detection and therapeutic targets for progressive pulmonary fibrosis.

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In addition to rare genetic variants and the locus, common genetic variants contribute to idiopathic pulmonary fibrosis (IPF) risk. The predictive power of common variants outside the locus for IPF and interstitial lung abnormalities (ILAs) is unknown. We tested the predictive value of IPF polygenic risk scores (PRSs) with and without the region on IPF, ILA, and ILA progression.

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Objectives: To evaluate methods of identifying patients with systemic sclerosis (SSc) using International Classification of Diseases, Tenth Revision (ICD-10) codes (M34*), electronic health record (EHR) databases and organ involvement keywords, that result in a validated cohort comprised of true cases with high disease burden.

Methods: We retrospectively studied patients in a healthcare system likely to have SSc. Using structured EHR data from January 2016 to June 2021, we identified 955 adult patients with M34* documented 2 or more times during the study period.

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  • The study aimed to explore the link between the severity of pneumonia seen on CT scans within six weeks of a COVID-19 diagnosis and the later emergence of lung abnormalities, known as post-COVID-19 lung abnormalities (Co-LA).
  • Researchers assessed 132 COVID-19 patients, finding that 32% developed Co-LA 6 to 24 months later, with a significant correlation between the severity of initial pneumonia and the likelihood of developing these lung issues—70% of those with extensive pneumonia progressed to Co-LA compared to just 17% with non-extensive pneumonia and none with no pneumonia.
  • The study concluded that greater pneumonia severity upon diagnosis increases the risk of developing long-term
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Background: Interstitial lung abnormalities (ILA) are CT findings suggestive of interstitial lung disease in individuals without a prior diagnosis or suspicion of ILD. Previous studies have demonstrated that ILA are associated with clinically significant outcomes including mortality. The aim of this study was to determine the prevalence of ILA in a large CT lung cancer screening program and the association with clinically significant outcomes including mortality, hospitalizations, cancer and ILD diagnosis.

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Purpose: To investigate the effect of vaccinations and boosters on the severity of COVID-19 pneumonia on CT scans during the period of Delta and Omicron variants.

Methods: Retrospectively studied were 303 patients diagnosed with COVID-19 between July 2021 and February 2022, who had obtained at least one CT scan within 6 weeks around the COVID-19 diagnosis (-2 to +4 weeks). The severity of pneumonia was evaluated with a 6-point scale Pneumonia Score.

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