Common exacerbation-prone phenotypes across asthma and chronic obstructive pulmonary disease (COPD)

xlomafota13 shared this article with you from Inoreader Common exacerbation-prone phenotypes across asthma and chronic obstructive pulmonary disease (COPD) Via Rhinitis by Kentaro Hyodo, Hironori Masuko, Hisayuki Oshima, Rie Shigemasa, Haruna Kitazawa, Jun Kanazawa, Hiroaki Iijima, Hiroichi Ishikawa, Takahide Kodama, Akihiro Nomura, Katsunori Kagohashi, Hiroaki Satoh, Takefumi Saito, Tohru Sakamoto, Nobuyuki Hizawa Background and objectives Chronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), are complex syndromes with diverse clinical symptoms due to multiple pathophysiological conditions. In this study, using common and shared risk factors for the exacerbation of asthma and COPD, we sought to clarify the exacerbation-prone phenotypes beyond disease labels, and to specifically investigate the role of the IL4RA gene polymorphism, which is related to type 2 inflammation, in these exacerbation-prone phenotypes. Methods The study population comprised patients with asthma (n = 117), asthma-COPD overlap (ACO; n = 37) or COPD (n = 48) and a history of exacerbation within the previous year. Cluster analyses were performed using factors associated with both asthma and COPD exacerbation. The association of the IL4RA gene polymorphism rs8832 with each exacerbation-prone phenotype was evaluated by multinomial logistic analyses usi ng non-asthma non-COPD healthy adults as controls (n = 1,529). In addition, the genetic influence of rs8832 was also examined in asthma patients with allergic rhinitis and no history of exacerbation (n = 130). Results Two-step cluster analyses identified five clusters that did not necessarily correspond to the diagnostic disease labels. Cluster 1 was characterized by high eosinophil counts, cluster 2 was characterized by smokers with impaired lung function, cluster 3 was characterized by the presence of gastroesophageal reflux, cluster 4 was characterized by non-allergic females, and cluster 5 was characterized by allergic rhinitis and elevated total immunoglobulin E levels. A significant association with rs8832 was observed for cluster 5 (odds ratio, 3.88 (1.34–11.26), p = 0.013) and also for the type 2 exacerbation-prone phenotypes (clusters 1 and 5: odds ratio, 2.73 (1.45–5.15), p = 1.9 × 10−3). Discussion Our results indicated that t he clinical heterogeneity of disease exacerbation may reflect the presence of common exacerbation-prone endotypes across asthma and COPD, and may support the use of the treatable traits approach for the prevention of exacerbations in patients with chronic inflammatory airway diseases. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hyperexcitability in adult mice with severe deficiency in NaV1.2 channels

xlomafota13 shared this article with you from Inoreader Hyperexcitability in adult mice with severe deficiency in Na<sub>V</sub>1.2 channels Via International Journal of Physiology, Pathophysiology and Pharmacology Int J Physiol Pathophysiol Pharmacol. 2022 Feb 15;14(1):55-59. eCollection 2022. ABSTRACT Epilepsy is one of the most common neurological diseases. Epileptic individuals are faced with seizures, which are largely caused by enhanced neuronal excitability and/or decreased neuronal inhibitory activity. SCN2A encodes a neuronal voltage-gated sodium channel, NaV1.2 that is primarily found in excitatory neurons throughout the brain. NaV1.2 is most concentrated within the principal neurons of the corticostriatal circuit, which includes pyramidal neurons in the medial prefrontal cortex and medium spiny neurons in the striatum. In the early stage of adult development, the NaV1.2 channel plays critical roles in generation and propagation of action potentials in these neurons. Gain of Function variants of SCN2A results in unprovoked seizures and epilepsy, while loss-of-function variants of SCN2A is a leading cause for autism spectrum disorder as well as intellectual disability. Previous studies have shown that full deletion of Scn2a gene in mice is lethal and partial disruption of Scn2a gene (less than 50%) leads to inhibition of neuronal excitability. A recent study from Dr. Yang's laboratory revealed an unexpected result from mice with severe NaV1.2 deficiency and they demonstrated that severe deletion of Scn2a gene (around 68% gene disruption) in NaV1.2 triggers neuronal hyperexcitability in adult mice. Their findings may explain the puzzling clinical observation that certain individuals with NaV1.2 deficiency still develop unprovoked seizure. With the knowledge that using sodium-channel blockers simply exacerbates the seizure, the need for understanding the intrinsic nature of the NaV1.2 channel provides an important research topic in the future. PMID:35310859 | PMC:PMC8918607 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Laboratory and imaging findings of necrotizing otitis externa are associated with pathogen type and disease outcome: A retrospective analysis

xlomafota13 shared this article with you from Inoreader Laboratory and imaging findings of necrotizing otitis externa are associated with pathogen type and disease outcome: A retrospective analysis Via ear nose throat Ear Nose Throat J. 2022 Mar 19:1455613221080973. doi: 10.1177/01455613221080973. Online ahead of print. ABSTRACT OBJECTIVE: To examine associations of laboratory and imaging data with diagnostic parameters of necrotizing otitis externa (NOE) and its severity, and to compare between bacterial and fungal infections. METHODS: Records of patients diagnosed with NOE during 2010-2018 at the Department of Otolaryngology, Head and Neck Surgery were reviewed retrospectively for demographics; disease characteristics; and laboratory, scintigraphy, and imaging results. RESULTS: Of 48 patients with NOE, the mean age is 73±11.6 years; 32 (67%) were males; 83% had diabetes mellitus. Common pathogens were pseudomonas (49%) and fungi (33%). Sensitivities of the technetium-scan (SPECT ratio ≥1.5), temporal bone computed tomography (CT), and gallium-scan (SPECT ratio ≥1.3) were: 78.7%, 48.8%, and 31.4%, respectively. Gallium-scan results correlated positively with CT bone involvement (p=0.002) and hospital length of stay (p=0.0014). C-reactive protein (CRP) level correlated with hospital length of stay (p=0.028) and positive technetium-scan results (p=0.012). Fungal infection had a higher technetium SPECT ratio (2.16 vs. 1.77, p=0.04), gallium SPECT ratio (1.4 vs. 1.2, p=0.02), longer duration of systemic treatment (87.4 vs. 37.9 days, p=0.014), and longer hospital length of stay (31.6 vs. 15.2 days, p=0.004) compared to non-fungal infection. Eight (17%) patients had responded poorly to treatment. Fungal pathogens, facial nerve paresis, extra-auricular, and bilateral disease were more prevalent among the non-responders. CONCLUSION: The technetium scan has higher sensitivity than temporal bone CT for diagnosing NOE. The gallium scan and CRP correlated well with hospital length of stay. A high rate of fungal infection was found, with significantly higher technetium and gallium SPECT ratios and worse outcome compared to bacterial infection. Fungal NOE remains therapeutically challenging. PMID:35311376 | DOI:10.1177/01455613221080973 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.