Browsing by Author "Ramakrishnan, Vijay"

Now showing 1 - 3 of 3
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    Impact of Airline Secondhand Tobacco Smoke Exposure on Respiratory Health and Lung Function Decades After Exposure Cessation
    (Elsevier, 2022) Diaz del Valle, Fernando; Zakrajsek, Jonathan K.; Min, Sung-Joon; Koff, Patricia B.; Bell, Harold W.; Kincaid, Keegan A.; Frank, Daniel N.; Ramakrishnan, Vijay; Ghosh, Moumita; Vandivier, R. William; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Background: Twenty-five percent to 45% of COPD is caused by exposures other than active smoking. Secondhand tobacco smoke (SHS) has been suggested as an independent cause of COPD, based on its association with increased respiratory symptoms and a small decrease in lung function, but its impact on respiratory health and lung function after exposure cessation has not been explored. Research question: What are the consequences of airline SHS exposure on respiratory health and lung function decades after cessation? Study design and methods: We performed a cohort study involving flight attendants because of their exposure to SHS that stopped > 20 years ago. We included subjects ≥ 50 years of age with > 1 year vs ≤ 1 year of airline SHS exposure (ie, exposed vs unexposed). Respiratory quality of life, as determined by the St. George's Respiratory Questionnaire (SGRQ), was the primary outcome for respiratory health. Key secondary outcomes included general quality of life (the Rand Corporation modification of the 36-item Short Form Health Survey Questionnaire; RAND-36), respiratory symptoms (COPD Assessment Test; CAT), and spirometry. Results: The study enrolled 183 SHS-exposed and 59 unexposed subjects. Exposed subjects were 66.7 years of age, and 90.7% were female. They were hired at 23.8 years of age, were exposed to airline SHS for 16.1 years, and stopped exposure 27.5 years before enrollment. Prior SHS exposure was associated with worsened SGRQ (6.7 units; 95% CI, 2.7-10.7; P = .001), RAND-36 physical and social function, and CAT vs unexposed subjects. SHS exposure did not affect prebronchodilator spirometry or obstruction, but was associated with lower postbronchodilator FEV1 and FEV1/FVC, total lung capacity, and diffusing capacity of the lungs for carbon monoxide in a subset of subjects. Former smoking and SHS exposure synergistically worsened SGRQ (β = 8.4; 95% CI, 0.4-16.4; P = .04). SHS exposure in people who never smoked replicated primary results and was associated with worsened SGRQ vs unexposed people (4.7 units; 95% CI, 0.7-7.0; P = .006). Interpretation: Almost three decades after exposure ended, airline SHS exposure is strongly and dose-dependently associated with worsened respiratory health, but less robustly associated with airflow abnormalities used to diagnose COPD.
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    Psychometric Properties of the Brief Version of the Questionnaire of Olfactory Disorders in Patients with Chronic Rhinosinusitis
    (Wiley, 2021) Mattos, Jose L.; Bodner, Todd E.; Mace, Jess C.; Schlosser, Rodney J.; Beswick, Daniel M.; Ramakrishnan, Vijay; Alt, Jeremiah; Payne, Spencer C.; Smith, Timothy L.; Soler, Zachary; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Background: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) is a 17-item instrument measuring olfactory-specific quality of life (QOL). However, in clinical research patients can be overwhelmed with multiple questionnaires. We recently developed the 7-item brief QOD-NS (B-QOD). Our objective was to evaluate the psychometric properties of the B-QOD in both the development (D) sample, and in a separate replication (R) sample. Methods: Testing on D (n = 203) and R (n = 281) samples included initial exploratory factor analysis (EFA), followed by internal reliability, information loss, and confirmatory factor analysis (CFA). Finally, incremental predictive utility analysis (IPUA) was performed by correlating the B-QOD with the 22-item Sino-Nasal Outcome Test (SNOT-22) survey. Results: EFAs of both D and R demonstrated an underlying single-factor structure (eigenvalue = 4.17 and 3.57, respectively) with comparable loading factors (R > 0.30 for both). B-QOD also had good internal reliability in both D and R (Cronbach's alpha = 0.88 and 0.83, respectively). Also, there is minimal information loss with B-QOD compared to QOD-NS in both D and R (R = 0.98 and 0.96, respectively). CFA indicates that the B-QOD single-factor model has good overall fit as measured by the Comparative Fit Index (CFI) and the Standardized Root Mean Squared Residuals (SRMSR) in the D and R samples (CFI = 0.99 and 0.97; SRMSR = 0.035 and 0.053). IPUA shows that the QOD-NS offers no additional predictive benefit of SNOT-22 scores when compared with B-QOD. Conclusion: The 7-item B-QOD captures a structurally coherent and reliable single dimension, with minimal information loss and excellent external predictive utility when compared to the QOD-NS.
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    Signatures for Viral Infection and Inflammation in the Proximal Olfactory System in Familial Alzheimer’s Disease
    (Elsevier, 2023) Bubak, Andrew N.; Merle, Laetitia; Niemeyer, Christy S.; Baxter, B. Dnate’; Gentile Polese, Arianna; Ramakrishnan, Vijay; Gomez, Johana; Madrigal, Lucia; Villegas-Lanau, Andres; Lopera, Francisco; Macklin, Wendy; Frietze, Seth; Nagel, Maria A.; Restrepo, Diego; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Alzheimer's disease (AD) is characterized by deficits in olfaction and olfactory pathology preceding diagnosis of dementia. Here we analyzed differential gene and protein expression in the olfactory bulb (OB) and tract (OT) of familial AD (FAD) individuals carrying the autosomal dominant presenilin 1 E280A mutation. Compared to control, FAD OT had increased immunostaining for β-amyloid (Aβ) and CD68 in high and low myelinated regions, as well as increased immunostaining for Iba1 in the high myelinated region. In FAD samples, RNA sequencing showed: (1) viral infection in the OB; (2) inflammation in the OT that carries information via entorhinal cortex from the OB to hippocampus, a brain region essential for learning and memory; and (3) decreased oligodendrocyte deconvolved transcripts. Interestingly, spatial proteomic analysis confirmed altered myelination in the OT of FAD individuals, implying dysfunction of communication between the OB and hippocampus. These findings raise the possibility that viral infection and associated inflammation and dysregulation of myelination of the olfactory system may disrupt hippocampal function, contributing to acceleration of FAD progression.