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1.
Pulm Med ; 2023: 6340851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38146504

RESUMO

Methods: We conducted a retrospective review of patients with pleural infection requiring intrapleural therapy at two tertiary referral centres. Results: We included 84 (62.2%) and 51 (37.8%) patients who received sequential and concurrent intrapleural therapy, respectively. Patient demographics and clinical characteristics, including age, RAPID score, and percentage of pleural opacity on radiographs before intrapleural therapy, were similar in both groups. Treatment failure rates (defined by either in-hospital mortality, surgical intervention, or 30-day readmission for pleural infection) were 9.5% and 5.9% with sequential and concurrent intrapleural therapy, respectively (p = 0.534). This translates to a treatment success rate of 90.5% and 94.1% for sequential and concurrent intrapleural therapy, respectively. There was no significant difference in the decrease in percentage of pleural effusion size on chest radiographs (15.1% [IQR 6-35.7] versus 26.6% [IQR 9.9-38.7], p = 0.143) between sequential and concurrent therapy, respectively. There were also no significant differences in the rate of pleural bleeding (4.8% versus 9.8%, p = 0.298) and chest pain (13.1% versus 9.8%, p = 0.566) between sequential and concurrent therapy, respectively. Conclusion: Our study adds to the growing literature on the safety and efficacy of concurrent intrapleural therapy in pleural infection.


Assuntos
Desoxirribonucleases , Doenças Pleurais , Ativador de Plasminogênio Tecidual , Estudos Retrospectivos , Estudos de Coortes , Doenças Pleurais/terapia , Ativador de Plasminogênio Tecidual/uso terapêutico , Desoxirribonucleases/uso terapêutico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Fibrinolíticos/uso terapêutico , Derrame Pleural/terapia
2.
Singapore Med J ; 2022 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-35366661

RESUMO

INTRODUCTION: The National Lung Screening Trial (NLST) identified individuals at high risk for lung cancer and showed that serial low-dose helical computer tomographic scans (CT) were able to identify lung cancer at an earlier stage and also demonstrated mortality reduction. However, there has been little evidence regarding the effectiveness of the Lung Cancer Screening Criteria in the Asian population. METHODS: To determine lung cancer patients who miss out on Lung Cancer screening criteria, we performed a retrospective audit from January to December 2018 in our hospital, and describe the characteristics of our patients diagnosed with lung cancer. RESULTS: We found that only 38.1% of the patients in our cohort who were diagnosed with lung cancer in 2018 fitted into NLST Criteria strictly by age and smoking criteria. However, those who fitted the inclusion criteria of lung cancer screening would derive significant benefits, as 85.4% presented at advanced stage and 54.6% did not survive one year. We explored using the United States Preventive Services Task Force criteria, which increased sensitivity to 58.7% of identifying our patients with diagnosed lung cancer. 15.5% of females with lung cancer in our cohort fitted into NLST Criteria, but their low smoking quantity is a significant contributing factor for females being excluded. CONCLUSION: Majority of Singapore patients diagnosed with lung cancer would not have been picked up by NLST Criteria, especially female patients. However, those who fitted the inclusion criteria would derive significant benefit, while expanding to an older limit may yield benefits with improved sensitivity.

3.
Singapore Med J ; 63(8): 426-432, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33721978

RESUMO

Introduction: Singapore's enhanced surveillance programme for COVID-19 identifies and isolates hospitalised patients with acute respiratory symptoms to prevent nosocomial spread. We developed risk prediction models to identify patients with low risk for COVID-19 from this cohort of hospitalised patients with acute respiratory symptoms. Methods: This was a single-centre retrospective observational study. Patients admitted to our institution's respiratory surveillance wards from 10 February to 30 April 2020 contributed data for analysis. Prediction models for COVID-19 were derived from a training cohort using variables based on demographics, clinical symptoms, exposure risks and blood investigations fitted into logistic regression models. The derived prediction models were subsequently validated on a test cohort. Results: Of the 1,228 patients analysed, 52 (4.2%) were diagnosed with COVID-19. Two prediction models were derived, the first based on age, presence of sore throat, dormitory residence, blood haemoglobin level (Hb), and total white blood cell counts (TW), and the second based on presence of headache, contact with infective patients, Hb and TW. Both models had good diagnostic performance with areas under the receiver operating characteristic curve of 0.934 and 0.866, respectively. Risk score cut-offs of 0.6 for Model 1 and 0.2 for Model 2 had 100% sensitivity, allowing identification of patients with low risk for COVID-19. Limiting COVID-19 screening to only elevated-risk patients reduced the number of isolation days for surveillance patients by up to 41.7% and COVID-19 swab testing by up to 41.0%. Conclusion: Prediction models derived from our study were able to identify patients at low risk for COVID-19 and rationalise resource utilisation.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Hospitalização , Modelos Logísticos , Estudos Retrospectivos , Hemoglobinas
4.
Chest ; 158(2): 512-522, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32184111

RESUMO

BACKGROUND: Chitinase activity is an important innate immune defence mechanism against infection that includes fungi. The 2 human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase are associated to allergy, asthma, and COPD; however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the association between chitinase activity, airway fungi and clinical outcomes in bronchiectasis and bronchiectasis-COPD overlap? STUDY DESIGN AND METHODS: A prospective cohort of 463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia, and Scotland) including individuals who were not diseased (n = 35) and who had severe asthma (n = 54), COPD (n = 90), bronchiectasis (n = 241) and BCO (n = 43). Systemic chitinase levels were assessed for bronchiectasis and BCO and related to clinical outcomes, airway Aspergillus status, and underlying pulmonary mycobiome profiles. RESULTS: Systemic chitinase activity is elevated significantly in bronchiectasis and BCO and exceed the activity in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (≥3 exacerbations/y). Subgroup analysis reveals an association between CHIT1 activity and the "frequent exacerbator" phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa that include Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asian patients with high CHIT1 may have potential roles in bronchiectasis exacerbations. INTERPRETATION: Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven "frequent exacerbators" with bronchiectasis in South-East Asian populations.


Assuntos
Povo Asiático , Bronquiectasia/sangue , Bronquiectasia/etnologia , Hexosaminidases/sangue , Aspergilose Pulmonar/sangue , Aspergilose Pulmonar/etnologia , Adulto , Idoso , Aspergillus , Asma/sangue , Asma/complicações , Asma/etnologia , Bronquiectasia/complicações , Feminino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Aspergilose Pulmonar/complicações , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/etnologia , Escócia , Singapura
5.
J Thorac Dis ; 9(3): 537-542, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28449460

RESUMO

BACKGROUND: Studies on diagnostic tests for exercise-induced bronchoconstriction (EIB) have centered around the asthmatic and elite athletic population. Traditionally, the exercise challenge test (ET) was recommended to assess EIB. We aimed to compare the performance of surrogate testing, mainly the hypertonic saline (HS) test, and methacholine challenge test (MCT) versus ET in identifying EIB among non-athletic subjects. METHODS: We prospectively recruited subjects who did not have confirmed active asthma, but who reported exercise-induced dyspnoea. The participants underwent HS and ET on separate days within two weeks. MCT performed within one year were obtained retrospectively from medical records. The sensitivity, specificity, and accuracy of each diagnostic test were calculated using ET as the gold standard. RESULTS: We recruited 27 participants (mean age 20.6±2.5 years; 92.6% male). Five (18.5%) had a history of self-reported asthma prior to recruitment. Eleven participants (40.7%) had a positive ET test. The sensitivity, specificity and accuracy of HS in diagnosing EIB was 90.9%, 62.5% and 74.1%; while that of MCT was 88.9%, 83.3% and 85.7% respectively. Six subjects were positive to HS but had negative ET test. CONCLUSIONS: Both HS and MCT were found to be suitable alternatives to ET in screening for EIB in the non-athletic population in this pilot study. Further large scale studies are required to confirm this finding. These tests have the potential to replace ET for the diagnosis of EIB in centres without ET equipment or facilities.

6.
Am J Respir Crit Care Med ; 190(12): 1430-6, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25390734

RESUMO

RATIONALE: Cigarette smoking is linked to important aspects of tuberculosis, such as susceptibility to infection, disease reactivation, mortality, transmission, and persistent infectiousness. The mechanistic basis for this remains poorly understood. OBJECTIVES: To compare the functional impairment seen in human alveolar macrophages (AM) from nonsmokers, smokers, and ex-smokers after infection with Mycobacterium tuberculosis (Mtb). METHODS: AM were acquired at bronchoscopy, and number and viability from smoking donors were compared with nonsmoking donors. AM were challenged in vitro with Mtb and intracellular bacterial viability was measured. Cytokine secretion was measured 24 hours postinfection by ELISA. Previously we determined the frequency of CD4(+)FoxP3(+) T cells in the presence or absence of allogeneic AM, and data were reanalyzed to separate the patient subjects according to smoking status. MEASUREMENTS AND MAIN RESULTS: There were significantly more AM from smokers compared with nonsmokers or ex-smokers (P < 0.01). AM from smokers could not control intracellular Mtb growth. Nonsmokers' AM generated significantly more tumor necrosis factor (TNF)-α, IFN-γ, and IL-1ß after Mtb infection compared with uninfected AM (P < 0.05). However, Mtb-infected AM from smokers did not secrete significantly more TNF-α, IFN-γ, and IL-1ß compared with uninfected smokers' AM. AM taken from ex-smokers also failed to secrete significantly increased TNF-α, IFN-γ, and IL-1ß after Mtb infection. Both smokers' and nonsmokers' AM induced FoxP3(+) T regulatory cell phenotype responses in allogeneic admixed T cells (>4.8 fold; P < 0.05). Even after Mtb infection, AM continued to drive this regulatory phenotype. CONCLUSIONS: In smokers, the pulmonary compartment has a number of macrophage-specific immune impairments that provide some mechanistic explanations whereby cigarette smoking renders a patient susceptible to tuberculosis infection and disease.


Assuntos
Pulmão/imunologia , Fumar/efeitos adversos , Tuberculose Pulmonar/etiologia , Idoso , Broncoscopia , Estudos de Casos e Controles , Citocinas/fisiologia , Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/imunologia , Citometria de Fluxo , Humanos , Imunidade Celular , Pulmão/microbiologia , Macrófagos Alveolares/fisiologia , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia
7.
PLoS One ; 7(6): e38488, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22675566

RESUMO

BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb) impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9) cells/l) was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb) or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s) were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG)- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as interfere with microbial eradication in the granuloma.


Assuntos
Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/patologia , Mycobacterium tuberculosis/imunologia , Transdução de Sinais , Linfócitos T/citologia , Tuberculose/imunologia , Tuberculose/microbiologia , Antígenos de Bactérias/imunologia , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Contagem de Linfócitos , Linfopenia/complicações , Linfopenia/epidemiologia , Linfopenia/imunologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Peso Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Prevalência , Transdução de Sinais/efeitos dos fármacos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Tuberculose/complicações , Tuberculose/epidemiologia , Fator de Necrose Tumoral alfa/farmacologia , Receptor fas/metabolismo
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