Research Articles (Pulmonology)
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- ItemRelationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection(American Society for Clinical Investigation, 2021-05) Riou, Catherine; Du Bruyn, Elsa; Stek, Cari; Daroowala, Remy; Goliath, Rene T.; Abrahams, Fatima; Said-Hartley, QonitaT cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2–specific (SARS-CoV-2–specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non–COVID-19 patients. We showed that SARSCoV- 2–specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1–mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARSCoV- 2–specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis–specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2–specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.
- ItemFourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosis(2020-01) Diacon, Andreas; De Jager, Veronique R; Dawson, RodneyBackground: Linezolid is increasingly used for the treatment of tuberculosis resistant to first-line agents, but the most effective dosing strategy is yet unknown. Methods: Between November 2014 and November 2016, we randomised 114 drug-sensitive treatment-naïve pulmonary tuberculosis patients from Cape Town, South Africa, to one of six 14-day treatment arms containing linezolid 300 mg once daily (qd), 300 mg twice daily (bd), 600 mg qd, 600 mg bd, 1200 mg qd, 1200 mg three times per week (tiw) or a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. Sixteen-hour sputum samples were collected overnight, and bactericidal activity characterized by the daily percentage change in time to positivity (TTP) and colony forming units (CFU). We also assessed the safety and pharmacokinetics of the study treatments. Results: Bactericidal activity increased with increasing doses of linezolid. Based on the daily percentage change in TTP, activity was highest for 1200 mg qd (4.5; 95% Bayesian confidence interval [BCI]: 3.3-5.6), followed by 600 mg bd (4.1; BCI: 2.5-5.7), 600 mg qd (4.1; BCI: 2.9-5.3), 300 mg bd (3.3; BCI: 1.9-4.7), 300 mg qd (2.3; BCI: 1.1-3.5) and 1200 mg tiw (2.2; BCI: 1.1-3.3). Similar results were seen with bactericidal activity characterized by the daily rate of change in CFU count. Antimycobacterial activity correlated positively with plasma drug exposure and percentage time over minimum inhibitory concentration. There were no unexpected adverse events. Conclusion: All linezolid doses showed bactericidal activity. For the same total daily dose, once daily dosing proved to be at least as effective as a divided twice daily dose. An intermittent dosing regimen, with 1200 mg given three times weekly, showed the least activity.
- ItemThe utility of hand-held mobile spirometer technology in a resource-constrained setting(Health & Medical Publishing Group, 2019) Du Plessis, E.; Swart, F.; Maree, D.; Heydenreich, J.; Van Heerden, J.; Esterhuizen, T. M.; Irusen, E. M.; Koegelenberg, C. F. N.Background. Mobile phone-linked spirometry technology has been designed specifically for evaluating lung function at primary care level. The Air-Smart Spirometer is the first mobile spirometer accepted in Europe for the screening of patients with chronic respiratory diseases. Objectives. To prospectively assess the accuracy of the device in measuring forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in a South African population, and to investigate the ability of the device to detect obstructive ventilatory impairment. Methods. A total of 200 participants were randomly assigned to perform spirometry with either the mobile spirometer connected to a smartphone or the desktop spirometer first, followed by the other. The FEV1/FVC ratio as well as the absolute FEV1 and FVC measurements were compared, using each participant as their own control. A Pearson correlation and Bland-Altman analysis were performed to measure the agreement between the two devices. We defined obstructive ventilatory impairment as FEV1/FVC <0.7 measured by desktop spirometry in order to calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Air-Smart Spirometer. Results. There was a strong correlation between the absolute FEV1 and FVC values and FEV1/FVC ratio measured with the mobile Air-Smart Spirometer and more conventional pulmonary function testing, with r=0.951, r=0.955 and r=0.898, respectively. The Air-Smart Spirometer had a sensitivity of 97.6%, specificity of 74.4%, PPV of 73.0% and NPV of 97.8% for obstructive ventilatory impairment. Conclusions. The mobile Air-Smart Spirometer compared well with conventional spirometry, making it an attractive and potentially affordable tool for screening purposes in a primary care setting. Moreover, it had a high sensitivity and NPV for obstructive ventilatory impairment.
- ItemRelationship between chest radiographic characteristics, sputum bacterial load, and treatment outcomes in patients with extensively drug-resistant tuberculosis(Elsevier, 2019) Te Riele, J. B.; Buser, V.; Calligaro, G.; Esmail, A.; Theron, G.; Lesosky, M.; Dheda, K.Background: Data about the relationship between chest radiographs and sputum bacillary load, with treatment outcomes, in patients with extensively drug-resistant tuberculosis (XDR-TB) from HIV/TB endemic settings are limited. Methods: Available chest radiographs from 97 South African XDR-TB patients, at the time of diagnosis, were evaluated by two independent readers using a validated scoring system. Chest radiograph findings were correlated with baseline sputum bacillary load (smear-grade and culture time-to-positive in MGIT), and prospectively ascertained clinical outcomes (culture conversion and all-cause mortality). Results: Radiographic bilateral lung disease was present in 75/97 (77%). In the multivariate analysis only a higher total radiographic score (95% CI) was associated with higher likelihood of death [1.16 (1.05–1.28) p = 0.003], and failure to culture convert [0.85 (0.74–0.97) p = 0.02]. However, when restricting analyses to HIV-infected patients, disease extent, cavitation, and total radiographic scores were not associated with mortality or culture-conversion. Finally, cavitary, disease extent, and total radiographic scores all positively correlated with bacterial load (culture time-to-positive). Conclusions: In endemic settings, XDR-TB radiological disease extent scores are associated with adverse clinical outcomes, including mortality, in HIV uninfected persons. These data may have implications for clinical and programmatic decision-making and for evaluation of new regimens in clinical trials.
- ItemAn endotracheal plasmablastic lymphoma(S. Karger AG, Basel, 2019) Bots, Eva M. T.; Opperman, Johan; Bassa, Fatima; Koegelenberg, Coenraad F. N.ENGLISH ABSTRACT: We describe an exceptionally rare case of a male patient with newly diagnosed advanced human immunodeficiency virus (HIV) infection, who presented with a plasmablastic lymphoma involving the right maxillary alveolar ridge with associated cervical lymphadenopathy. On a staging positron emission tomography computed tomography (PET-CT) scan, he was incidentally found to have an endotracheal tumour involving the anterolateral aspect of the mid-trachea. The tumour appeared to be well-vascularised at bronchoscopy and was confirmed as well-differentiated plasmablastic lymphoma. Plasmablastic lymphoma is a rare form of non-Hodgkin lymphoma and is associated with HIV. Tracheal involvement to the extent seen in our patient is exceptionally rare, and, to the best of our knowledge, has never been described.