Pulmonary Medicine

Mathai, S. K., J. Cardwell, F. Metzger, J. Powers, A. D. Walts, J. A. Kropski, O. Eickelberg, S. M. Hauck, I. V. Yang and D. A. Schwartz (2020). “Preclinical Pulmonary Fibrosis (PrePF) Circulating Protein Biomarkers.” Am J Respir Crit Care Med Aug 5. [Epub ahead of print.].

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Idiopathic pulmonary fibrosis (IPF) is characterized by progressive, irreversible scarring of the lung parenchyma that can require invasive diagnostic testing. Interstitial lung abnormalities (ILA) have been described in the general population. Among asymptomatic first-degree relatives of Familial Interstitial Pneumonia (FIP) patients, 14% have radiologic ILA and 35% have interstitial abnormalities on biopsy. In the Framingham population, fibrotic ILA were present in 1.8% of subjects ≥50 years of age and associated with increased risk of death (5, 6), suggesting ILA may be a harbinger of IPF. [No abstract; excerpt from article].

Defayette, A., A. Perrello, T. Brewer, J. Picano and S. Ahmed (2020). “Enteral baclofen withdrawal managed with intravenous dexmedetomidine: A case report.” Am J Health Syst Pharm Jan 13. [Epub ahead of print].

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PURPOSE: Acute enteral baclofen withdrawal can be clinically severe if not identified and managed appropriately. Treatment of baclofen withdrawal includes supportive care and reinitiation of baclofen. There are limited pharmacotherapeutic interventions available to manage symptoms of acute enteral baclofen withdrawal, especially in nonintubated patients. SUMMARY: We describe a 61-year-old Caucasian male with a past medical history of chronic back pain and spinal stenosis who was admitted to the medical intensive care unit with confusion, insomnia, agitation, delirium, and auditory and visual hallucinations. For control of agitation, the patient was administered 10 mg of i.v. haloperidol, 1 mg of i.v. lorazepam, and 14 mg of i.v. midazolam, with minimal improvement noted; therefore, dexmedetomidine was initiated, which led to clinical resolution of his symptoms. Upon further investigation it was determined that the patient was taking approximately 10 baclofen 20-mg tablets a day. According to his pharmacy records, he had filled prescriptions for a total of 738 baclofen tablets in the previous 12 weeks. The patient’s presentation and sudden discontinuation of high-dose baclofen led to a diagnosis of baclofen withdrawal. Baclofen was subsequently restarted, and dexmedetomidine was weaned over 36 hours. CONCLUSION: Dexmedetomidine controlled this patient’s agitation and delirium without suppressing his respiratory drive and should be considered for management of acute enteral baclofen withdrawal.

Tague, L. K., D. E. Byers, R. Hachem, D. Kreisel, A. S. Krupnick, H. S. Kulkarni, C. Chen, H. J. Huang and A. Gelman (2020). “Impact of SLCO1B3 polymorphisms on clinical outcomes in lung allograft recipients receiving mycophenolic acid.” Pharmacogenomics J 20(1): 69-79.

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Single-nucleotide polymorphisms (SNPs) in genes involved in mycophenolic acid (MPA) metabolism have been shown to contribute to variable MPA exposure, but their clinical effects are unclear. We aimed to determine if SNPs in key genes in MPA metabolism affect outcomes after lung transplantation. We performed a retrospective cohort study of 275 lung transplant recipients, 228 receiving mycophenolic acid and a control group of 47 receiving azathioprine. Six SNPs known to regulate MPA exposure from the SLCO, UGT and MRP2 families were genotyped. Primary outcome was 1-year survival. Secondary outcomes were 3-year survival, nonminimal (>/=A2 or B2) acute rejection, and chronic lung allograft dysfunction (CLAD). Statistical analyses included time-to-event Kaplan-Meier with log-rank test and Cox regression modeling. We found that SLCO1B3 SNPs rs4149117 and rs7311358 were associated with decreased 1-year survival [rs7311358 HR 7.76 (1.37-44.04), p = 0.021; rs4149117 HR 7.28 (1.27-41.78), p = 0.026], increased risk for nonminimal acute rejection [rs4149117 TT334/T334G: OR 2.01 (1.06-3.81), p = 0.031; rs7311358 GG699/G699A: OR 2.18 (1.13-4.21) p = 0.019] and lower survival through 3 years for MPA patients but not for azathioprine patients. MPA carriers of either SLCO1B3 SNP had shorter survival after CLAD diagnosis (rs4149117 p = 0.048, rs7311358 p = 0.023). For the MPA patients, Cox regression modeling demonstrated that both SNPs remained independent risk factors for death. We conclude that hypofunctional SNPs in the SLCO1B3 gene are associated with an increased risk for acute rejection and allograft failure in lung transplant recipients treated with MPA.

Mathai, S. K., S. Humphries, J. A. Kropski, T. S. Blackwell, J. Powers, A. D. Walts, C. Markin, J. Woodward, J. H. Chung, K. K. Brown, M. P. Steele, J. E. Loyd, M. I. Schwarz, T. Fingerlin, I. V. Yang, D. A. Lynch and D. A. Schwartz (2019). “Muc5b Variant Is Associated with Visually and Quantitatively Detected Preclinical Pulmonary Fibrosis.” Thorax Sep 26. [Epub ahead of print].

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BACKGROUND: Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT. METHODS: First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in MUC5B and TERT was performed. FINDINGS: In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95% CI 0.72 to 0.89) and 86% sensitivity (95% CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex. INTERPRETATION: PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities.

Mageto, Y. (2019). “The Increasing Use of Social Media for Medical Information: Should Healthcare Providers Be Concerned?” Ann Am Thorac Soc 16(5): 544-546.

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During the last decade, social media use among adults in the United States has increased exponentially. Intuitively, we might assume that the increase in use primarily involves Gen Xers (born 1965–1980) and younger generations. However, Traditionalists (born 1900–1945) and Baby Boomers (born 1946–1964) have also been noted to have a significant uptick in their use of social media. Usage has increased from 2% in 2005 to 25% in 2015. Many members of this generation have become increasingly savvy with their smartphones, using them to record conversations in physician’s offices as well as looking up information on the Internet. The most commonly used platforms are Facebook, Google, and YouTube. These same generations (Traditionalists and Baby Boomers) have increasingly turned to the Internet, accessing websites, viewing videos, and discussing their medical information online with other patients, caregivers, and anyone else who desires to chime in. YouTube and other web media platforms were never designed as a platform for medical research or medical education, but by default, they have become a platform for reporting/sharing research, medical education, and patient support. This invites the question: Why should we be concerned about what is posted on YouTube? If one simply views it as an entertainment platform, then it should not be an issue. But because it has become a platform for healthcare, it is past time to have additional discussions/research going forward, developing tools to assess content and use of said content, and holding those who post inaccurate and harmful information accountable. (Excerpt from text, p. 544; no abstract available.)