Publications by authors named "Michael P Combs"

Background: The ScanCLAD study reported a lower incidence of chronic lung allograft dysfunction (CLAD) with the use of once-daily tacrolimus vs twice-daily cyclosporine. Using the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant (TTX) Registry data, we evaluated the hypothesis that tacrolimus is superior to cyclosporine in real-world clinical practice.

Methods: This study is a retrospective cohort study of adult lung transplant recipients in the ISHLT registry from January 1, 2000, to June 30, 2018, with known CLAD status.

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Background: Chronic lung allograft dysfunction (CLAD) is the leading long-term cause of poor outcomes after transplant and manifests by fibrotic remodeling of small airways and/or pleuroparenchymal fibroelastosis. This study evaluated the effect of pirfenidone on quantitative radiographic and pulmonary function assessment in patients with CLAD.

Methods: We performed a single-center, 6-month, randomized, placebo-controlled trial of pirfenidone in patients with CLAD.

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Background: Lung transplantation remains the sole curative option for patients with idiopathic pulmonary fibrosis (IPF), but donor organs remain scarce, and many eligible patients die before transplant. Tools to optimize the timing of transplant referrals are urgently needed.

Methods: Least absolute shrinkage and selection operator was applied to clinical and proteomic data generated as part of a prospective cohort study of interstitial lung disease (ILD) to derive clinical, proteomic, and multidimensional logit models of near-term death or lung transplant within 18 months of blood draw.

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Chronic lung allograft dysfunction (CLAD) is the leading cause of death after lung transplant, and azithromycin has variable efficacy in CLAD. The lung microbiome is a risk factor for developing CLAD, but the relationship between lung dysbiosis, pulmonary inflammation, and allograft dysfunction remains poorly understood. Whether lung microbiota predict outcomes or modify treatment response CLAD is unknown.

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Article Synopsis
  • Idiopathic pulmonary fibrosis (IPF) is characterized by ongoing tissue damage and scarring in the lungs, driven by persistent activation of mesenchymal cells related to various signaling pathways.
  • The study focuses on the role of the transcription factor NFAT1, which controls a key profibrotic mediator (autotaxin) in lung mesenchymal cells, finding that mice lacking NFAT1 have improved survival and less lung fibrosis after injury.
  • The research indicates that NFAT1 activates profibrotic processes in IPF and suggests it could be a potential target for therapeutic intervention in treating the disease.
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Background: Small airway inflammation and fibrosis or bronchiolitis obliterans (BO) is the predominant presentation of chronic lung allograft dysfunction (CLAD) post-lung transplantation. Carbon monoxide (CO) is a critical endogenous signaling transducer with known anti-inflammatory and anti-fibrotic effects but its therapeutic potential in CLAD remains to be fully elucidated.

Methods: Here we investigate the effect of inhaled CO in modulating chronic lung allograft rejection pathology in a murine orthotopic lung transplant model of BO (B6D2F1/J→DBA/2J).

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A 30-year-old woman was referred with increasing shortness of breath and cough in the setting of GATA2 deficiency. She initially presented 9 years previously with recurrent episodes of pneumonia and sinusitis. Genetic testing revealed a heterozygous GATA2 mutation (c.

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Chronic lung allograft dysfunction (CLAD) results in significant morbidity after lung transplantation. Potential CLAD occurs when lung function declines to 80-90% of baseline. Better noninvasive tools to prognosticate at potential CLAD are needed.

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Background: Alterations in the respiratory microbiome are common in chronic lung diseases, correlate with decreased lung function, and have been associated with disease progression. The clinical significance of changes in the respiratory microbiome after lung transplant, specifically those related to development of chronic lung allograft dysfunction (CLAD), are unknown. The aim of this study was to evaluate the effect of lung microbiome characteristics in healthy lung transplant recipients on subsequent CLAD-free survival.

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Article Synopsis
  • Understanding the mechanisms behind allograft fibrosis and chronic graft failure is crucial for improving transplant outcomes, particularly in cases of restrictive allograft syndrome (RAS).
  • Researchers used a specific lung transplant model to show that humoral immune responses, especially involving B cells, play a significant role in developing RAS.
  • Findings indicated that blocking B cell activity reduced fibrosis in lung allografts, suggesting targeted therapies could improve management of different types of chronic lung allograft dysfunction.
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Article Synopsis
  • Histopathologic studies indicate that chronic lung allograft dysfunction (CLAD) involves inflammation from mononuclear cells (MNC) and growth from mesenchymal cells (MC), with interleukin 6 (IL-6) playing a key role in their interaction.
  • Analysis of bronchoalveolar lavage fluid shows that IL-6 and its receptor levels are significantly higher in CLAD-affected lungs compared to before the onset of the disease.
  • Research suggests that MNCs increase IL-6 production when interacting with MCs, leading to enhanced MC activity and fibrosis, while experiments on mice demonstrate that blocking IL-6 can significantly reduce lung fibrosis.
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Background: Poor sleep is common in the ICU setting and may represent a modifiable risk factor for patient participation in ICU-based physical therapy (PT) interventions. This study evaluates the association of perceived sleep quality, delirium, sedation, and other clinically important patient and ICU factors with participation in physical therapy (PT) interventions.

Method: This was a secondary analysis of a prospective observational study of sleep in a single academic medical ICU (MICU).

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Objective: To describe the extent to which US physicians endorse substituted judgments in principle or accommodate them in practice.

Patients And Methods: We surveyed a stratified, random sample of 2016 physicians by mail from June 25, 2010, to September 3, 2010. Primary outcome measures were agreement with 2 in-principle statements about substituted judgment and, after an experimental vignette that varied the basis used by a patient's surrogate to refuse life-saving treatment, responses indicating how appropriate it would be to overrule the surrogate's decision.

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Background: Regarding controversial medical services, many have argued that if physicians cannot in good conscience provide a legal medical intervention for which a patient is a candidate, they should refer the requesting patient to an accommodating provider. This study examines what US physicians think a doctor is obligated to do when the doctor thinks it would be immoral to provide a referral.

Method: The authors conducted a cross-sectional survey of a random sample of 2000 US physicians from all specialties.

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