Dessmon Y.H. Tai

Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome

BackgroundSevere acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls.ResultsThe number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis.ConclusionsThis differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.

Expanding ICU facilities in an epidemic: recommendations based on experience from the SARS epidemic in Hong Kong and Singapore

AbstractEpidemics have the potential to severely strain intensive care resources and may require an increase in intensive care capability. Few intensivists have direct experience of rapidly expanding intensive care services in response to an epidemic. This contribution presents the recommendations of an expert group from Hong Kong and Singapore who had direct experience of expanding intensive care services in response to the epidemic of severe acute respiratory syndrome. These recommendations cover training, infection control, staffing, communication and ethical issues. The issue of what equipment to purchase is not addressed. Early preparations should include fit testing of negative pressure respirators, training of reserve staff, sourcing of material for physical modifications to the ICU, development of infection control policies and training programmes, and discussion of triage and quarantine issues.

Large artery ischaemic stroke in severe acute respiratory syndrome (SARS).

Abstract.Of the 206 patients who contracted Severe Acute Respiratory Syndrome (SARS) in Singapore five developed large artery cerebral infarctions. Four patients were critically-ill and three died. Intravenous immunoglobulin was given to three patients. An increased incidence of deep venous thrombosis and pulmonary embolism was also observed among the critically-ill patients. We believe our experience warrants an increased vigilance against stroke and other thrombotic complications among critically-ill SARS patients in future outbreaks, especially if treatment such as intravenous immunoglobulin, that increases pro-thrombotic tendency, is contemplated.

Timeliness of diagnosing lung cancer: Number of procedures and time needed to establish diagnosis

Abstract To study number of procedures and time to diagnose lung cancer and factors affecting the timeliness of clinching this diagnosis. Retrospective cohort study of lung cancer patients who consecutively underwent diagnostic bronchoscopy in 1 year (October 2013 to September 2014). Out of 101 patients diagnosed with lung cancer from bronchoscopy, average time interval between first abnormal computed tomogram (CT) scan-to-1st procedure, 1st procedure-to-diagnosis, and 1st abnormal CT scan-to-diagnosis was 16 ± 26, 11 ± 19, and 27 ± 33 days, respectively. These intervals were significantly longer in those requiring repeat procedures. Multivariate analysis revealed inconclusive 1st procedure to be the predictor of prolonged (>30 days) CT scan to diagnosis time (P = 0.04). Twenty-nine patients (28.7%) required repeat procedures (n = 63). Reasons behind repeating the procedures were inadequate procedure (n = 14), inaccessibility of lesion (n = 9), inappropriate procedure (n = 5), mutation analysis (n = 2), and others (n = 2). Fifty had visible endo-bronchial lesion, 20 had positive bronchus sign, and 83 had enlarged mediastinal/hilar lymph-nodes or central masses adjacent to the airways. Fewer procedures, and shorter procedure to diagnosis time, were observed in those undergoing convex probe endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) (P = 0.04). Most patients exhibit enlarged mediastinal lymph node or mass adjacent to the central airway accessible by convex probe EBUS-TBNA. Hence, combining it with conventional bronchoscopic techniques such as bronchoalveolar lavage, brush, and forceps biopsy increases detection rate, and reduces number of procedures and time to establish diagnosis. This may translate into cost and resource savings, timeliness of diagnosis, greater patient satisfaction, and conceivably better outcomes.

Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion

AbstractTo study the performance of serum and pleural lactate dehydrogenase (LDH) level in predicting survival in patients with adenocarcinoma lung presenting with malignant pleural effusions (MPE) at initial diagnosis.Retrospective cohort study of the patient hospitalized for adenocarcinoma lung with MPE in year 2012.Univariate analyses showed lower pleural fluid LDH 667 (313–967) versus 971 (214–3800), P = 0.04, female gender 9 (100%) versus 27 (41.5%), P = 0.009, never smoking status 9 (100%) versus 36 (55.3%), P = 0.009, and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy 8 (89%) versus 26 (40%), P = 0.009 to correlate with survival of more than 1.7 year versus less than 1.7 year. In multivariate analysis, low pleural fluid LDH and female gender maintained significance. The pleural LDH level of ⩽1500 and >1500 U/L discriminated significantly (P = 0.009) between survival.High pleural LDH (>1500 IU/L) predicts shorter survival (less than a year) in patients with adenocarcinoma lung presenting with MPE at the time of initial diagnosis. This marker may be clinically applied for selecting therapeutic modality directed at prevention of reaccumulation of MPE. Patients with low pleural LDH may be considered suitable for measures that provide more sustained effect on prevention of reaccumulation such as chemical pleurodesis or tunneled pleural catheter.

Experience With the Use of Single-Use Disposable Bronchoscope in the ICU in a Tertiary Referral Center of Singapore

Background: Flexible bronchoscopy is performed frequently in intensive care units (ICUs) for various indications using the reusable conventional bronchoscope (CB). Recently, “single-use disposable bronchoscope” (SB) was introduced into the health care industry. The purpose of this study was to compare the utility of SB with CB in ICU. Methods: A retrospective review of medical records of patients undergoing flexible bronchoscopy in the ICUs in the year 2015. Results: Ninety-three patients undergoing flexible bronchoscopy in the ICU were studied. Eighty-three bronchoscopies were performed using SB in 71 patients, and 24 using CB in 22 patients. The most common indications for using the SB were percutaneous tracheostomy [n=37 (44.6%)] in neuro-ICU, followed by collecting specimens for microbiological evaluation [n=20 (24.1%)] in the medical ICU. Airway inspection [8 (9.6%)], bronchial toilet [8 (9.6%)], hemoptysis [5 (6%)], and intubation [3 (3.6%)] were other indications for which SB was used. Microbiological yield of SB was 70% (14/20) versus 70% (7/10) for CB (P=1.0). The median interval between identification of the need-to-start of the procedure was shorter with SB (10 min) versus CB (66 min, P=0.01), whereas the cost was similar, SGD450 versus SGD472, respectively. In addition, less (3 personnel) were needed to perform bronchoscopy with SB versus 5 with CB with additional resource sparing effect in terms of nursing personnel having to wheel the CB equipment to ICU. Conclusions: SB is equivalent in performance to CB in ICU. In addition, the SB may confer clinical, economic, and logistical advantages over the CB.

Significance of coexistent granulomatous inflammation and lung cancer

Aims Coexistence of lung cancer and granulomatous inflammation in the same patient confuses clinicians. We aimed to document the prevalence, clinicopathological features, treatment outcomes and prognosis in patients with coexisting granulomatous inflammation undergoing curative lung resection for lung cancer, in a tuberculosis (TB)-endemic country. Methods An observational cohort study of patients with lung cancer undergoing curative resection between 2012 and 2015 in a tertiary centre in Singapore. Results One hundred and twenty-seven patients underwent lung resection for cancer, out of which 19 (14.9%) had coexistent granulomatous inflammation in the resected specimen. Median age was 68 years and 58.2% were males. Overall median (range) survival was 451 (22–2452) days. Eighteen (14%) patients died at median duration of 271 days after surgery. The postsurgery median survival for those alive was 494 (29–2452) days in the whole group. Subgroup analysis did not reveal any differences in age, gender, location of cancer, radiological features, type of cancer, chemotherapy, history of TB or survival in patients with or without coexistent granulomatous inflammation. Conclusions Incidental detection of granulomatous inflammation in patients undergoing lung resection for cancer, even in a TB-endemic country, may not require any intervention. Such findings may be due to either mycobacterial infection in the past or ‘sarcoid reaction’ to cancer. Although all patients should have their resected specimen sent for acid-fast bacilli culture and followed up until the culture results are reported, the initiation of the management of such patients as per existing lung cancer management guidelines does not affect their outcome adversely.

Role of Bronchoscopy in Prompt Discharge From the Intensive Care Unit.

Background:Intensive care unit (ICU) stays are 2.5 times more costly than other hospital stays, and 93.3% of ICU use is for respiratory disease with ventilator support. The aim of this study was to assess the role of bronchoscopy on discontinuation of mechanical ventilation, and prompt discharge from ICU in our institution. Methods:Retrospective review of medical records of patients referred for bronchoscopic intervention for acute respiratory failure from malignant or benign central airway diseases requiring ICU admission. Results:Twelve critically ill patients were studied. Median (range) age was 63 years (range, 35 to 85 y). Nine (75%) had endotracheal tube, and 3 (25%) had tracheostomy tube. Nine (75%) of 12 patients admitted to ICU could be transferred to general ward after median (range) interval of 2 days (range, 1 to 7 d) after the day of intervention. Median (range) prebronchoscopy and postbronchoscopy PaO2/FiO2 ratio was 102.8 (range, 99.2 to 328) and 180 (range, 129 to 380), respectively, with significant improvement postintervention (P=0.002). Radiologically, all 8 patients with lung atelectasis on presentation experienced complete reexpansion of the lung on the day after bronchoscopic intervention. Conclusion:The majority of patients in our cohort (75%) of benign and malignant etiology could be promptly (within 2 d postbronchoscopy) transferred out from ICU to general ward after successful discontinuation of mechanical ventilation and extubation after bronchoscopic intervention. We advocate early recognition and bronchoscopic intervention in suitable patients.

Outcome of advanced lung cancer with central airway obstruction versus without central airway obstruction

Patients with central airway obstruction (CAO) from advanced lung cancer present with significant morbidity and are assumed to have lower survival. Hence, they are offered only palliative support. We asked if patients who have advanced lung cancer with CAO (recanalised and treated) will behave similarly to those with advanced lung cancer without CAO. This study was a retrospective review of the medical records of the patients managed for advanced lung cancer during 2010 and 2015 at our institution. 85 patients were studied. Median survival and 1-, 2- and 5-year survival were 5.8 months, 30.3%, 11.7% and 2.3% versus 9.3 months, 35.7%, 9.6% and 4.7%, respectively, in the CAO and no CAO groups (p=0.30). More patients presented with respiratory failure (15 (35%) versus none; p=0.0001) and required assisted mechanical ventilation (10 (23.3%) versus none; p=0.001) in the CAO group compared with the no CAO group. Fewer patients received chemotherapy in the CAO group (11 (25.5%)) compared with the no CAO group (23 (54.7%); p=0.008). There was no difference in survival among patients with advanced lung cancer whether they presented with CAO or without CAO. Survival was similar to those without CAO in patients with recanalised CAO despite greater morbidity and lesser use of chemotherapy, strongly advocating bronchoscopic recanalisation of CAO. These findings dispel the nihilism associated with such cases. Survival is similar among patients with advanced lung cancer whether they present with CAO or without CAO http://ow.ly/djRE30iDH6V

Our Clinical Experience of Self-Expanding Metal Stent for Malignant Central Airway Obstruction

Background We studied the safety, effectiveness, and limitations of airway stenting using self-expanding metal stent (SEMS) in patients with malignant central airway obstruction (CAO). Methods A retrospective review of records of patients undergoing SEMS placement for malignant CAO during year 2013 - 2014 was done. Results Sixteen patients (11 males and five females) underwent SEMS placement for malignant CAO. Median (range) age was 66 (54 - 78) years. No perioperative or immediate postoperative complications were seen except acute myocardial infarction (AMI) in one patient. Three patients were transferred to intensive care unit (ICU) for closer monitoring after the procedure and were discharged the next day. All four patients with lung atelectasis on presentation experienced complete re-expansion of the lung post-stenting. The dyspnea was substantially relieved in 14 (87.5%) patients. Two of the three patients who had been intubated were weaned off from the ventilator following stent insertion. Stent patency was maintained until death in all patients except one. Median survival from the date of diagnosis and the date of stent placement in lung cancer, esophageal cancer, and thyroid cancer were 140 (21 - 564) and 85 (15 - 361), 288 (80 - 419) and 61 (60 - 171), and 129 (71 - 187) and 67 (16 - 118) days, respectively. This survival was similar to reported expected survival associated with the underlying malignancy. During follow-up, granulation tissue (n = 1), mucostasis (n = 1), and tumor ingrowth (n = 2) were the most frequently encountered complications. Conclusion SEMSs are safe and effective in reversing respiratory failure caused by malignant CAO, averting premature death, allowing application of cancer targeted therapy, and restoring impending shortened survival to expected life expectancy associated with the underlying malignancy.