Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease.

BACKGROUND AND PURPOSE: Corticosteroid resistance poses a major barrier to an effective anti-inflammatory therapy for chronic obstructive pulmonary disease (COPD). The present study aimed to investigate potential corticosteroid re-sensitization actions of andrographolide, a bioactive molecule from the herb Andrographis paniculata, in COPD models, particularly in peripheral blood mononuclear cells (PBMCs) from COPD patients. EXPERIMENTAL APPROACH: Corticosteroid sensitivity in PBMCs collected from COPD patients, or in human monocytic U937 cells exposed to cigarette smoke extract (CSE), was determined by measuring LPS-induced IL-8 production, in the presence and absence of andrographolide. The mechanisms of corticosteroid re-sensitization action of andrographolide were evaluated in a mouse cigarette smoke (CS)-induced acute lung injury model. KEY RESULTS: Impaired inhibition of IL-8 production by dexamethasone was detected in PBMCs from COPD patients and in CSE-exposed U937 cells, together with reduced levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and histone deacetylase-2 (HDAC2). In both PBMCs and CSE-exposed U937 cells, andrographolide restored dexamethasone inhibition of IL-8 production, accompanied by the up-regulation of Nrf2 and HDAC2 levels. In the U937 cells, andrographolide was able to block CSE-induced Akt and reduce the level of c-Jun. Besides, andrographolide also augmented dexamethasone actions on lowering total and neutrophil counts, cytokine levels, and oxidative damage markers in bronchoalveolar lavage fluid from CS-exposed mice. CONCLUSION AND IMPLICATIONS: We report here for the first time a novel corticosteroid re-sensitization property of andrographolide in human PBMCs and provide mechanistic evidence to support clinical evaluation of andrographolide in reversing steroid resistance in COPD.

An evaluation of inhaled antibiotic liposome versus antibiotic nanoplex in controlling infection in bronchiectasis.

Inhaled antibiotic nanoparticles have emerged as an effective strategy to control infection in bronchiectasis lung owed to their mucus-penetrating ability. Using ciprofloxacin (CIP) as the model antibiotic, we evaluated dry powder inhaler (DPI) formulations of two classes of antibiotic nanoparticles (i.e. liposome and nanoplex) in their (1) physical characteristics (i.e. size, zeta potential, CIP payload, preparation efficiency), (2) dissolution in artificial sputum medium, (3) ex vivo mucus permeability, (4) antimicrobial activity against Pseudomonas aeruginosa in mucus, (5) cytotoxicity towards human lung epithelium cells, and (6) in vitro aerosolization efficiency. The results showed that the CIP nanoplex exhibited fast dissolution with CIP supersaturation generation, in contrast to the slower release of the liposome (80 versus 30% dissolution after 1 h). Both nanoparticles readily overcame the mucus barrier attributed to their nanosize and mucus-inert surface (50% permeation after 1 h), leading to their similarly high antipseudomonal activity. The CIP liposome, however, possessed much lower CIP payload than the nanoplex (84% versus 3.5%), resulting in high lipid contents in its DPI formulation that led to higher cytotoxicity and lower aerosolization efficiency. The CIP nanoplex thus represented a superior formulation owed to its simpler preparation, higher CIP payload hence lower dosage, better aerosolization, and lower cytotoxicity.

A new therapeutic avenue for bronchiectasis: Dry powder inhaler of ciprofloxacin nanoplex exhibits superior ex vivo mucus permeability and antibacterial efficacy to its native ciprofloxacin counterpart.

Non-cystic fibrosis bronchiectasis (NCFB) characterized by permanent bronchial dilatation and recurrent infections has been clinically managed by long-term intermittent inhaled antibiotic therapy among other treatments. Herein we investigated dry powder inhaler (DPI) formulation of ciprofloxacin (CIP) nanoplex with mannitol/lactose as the excipient for NCFB therapy. The DPI of CIP nanoplex was evaluated against DPI of native CIP in terms of their (1) dissolution characteristics in artificial sputum medium, (2) ex vivo mucus permeability in sputum from NCFB and healthy individuals, (3) antibacterial efficacy in the presence of sputum against clinical Pseudomonas aeruginosa strains (planktonic and biofilm), and (4) cytotoxicity towards human lung epithelial cells. Despite their similarly fast dissolution rates in sputum, the DPI of CIP nanoplex exhibited superior mucus permeability to the native CIP (5-7 times higher) attributed to its built-in ability to generate highly supersaturated CIP concentration in the sputum. The superior mucus permeability led to the CIP nanoplex's higher antibacterial efficacy (>3 log10 CFU/mL). The DPI of CIP nanoplex exhibited similar cytotoxicity towards the lung epithelial cells as the native CIP indicating its low risk of toxicity. These results established the promising potential of DPI of CIP nanoplex as a new therapeutic avenue for NCFB.

Profiling non-tuberculous mycobacteria in an Asian setting: characteristics and clinical outcomes of hospitalized patients in Singapore.

BACKGROUND: Non-tuberculous mycobacteria (NTM) infection is an increasing problem worldwide. The epidemiology of NTM in most Asian countries is unknown. This study investigated the epidemiology, and clinical profile of inpatients in whom NTM was isolated from various anatomical sites in a Singaporean population attending a major tertiary referral centre. METHODS: Demographic profile, clinical data, and characteristics of patients hospitalized with NTM isolates at a major tertiary hospital over two-year period were prospectively assessed (2011-2012). Data collected included patient demographics, ethnicity, smoking status, co-morbidities, NTM species, intensive care unit (ICU) treatment, and mortality. RESULTS: A total of 485 patients (62.1% male) with 560 hospital admissions were analysed. The median patient age was 70 years. Thirteen different NTM species were isolated from this cohort. Mycobacterium abscessus (M. abscessus) (38.4%) was most frequently isolated followed by Mycobacterium fortuitum (M. fortuitum) (16.6%), Mycobacterium avium complex (MAC) (16.3%), Mycobacterium kansasii (M. kansasii) (15.4%), and Mycobacterium gordonae (M. gordonae) (6.8%). Most (91%) NTM was isolated from the respiratory tract. The three most common non-pulmonary sites were; blood (2.7%), skin wounds and abscesses (2.1%), and gastric aspirates (1.1%). A third (34.4%) of the study population had prior pulmonary tuberculosis (PTB). There was a significant association between isolated NTM species, and patient age (p = 0.0002). Eleven (2.2%) patients received intensive care unit (ICU) treatment during the study period and all cause mortality within 1 year of the study was 16.9% (n = 82). Of these, 72 (87.8%) patients died of pulmonary causes. CONCLUSIONS: The profile of NTM species in Singapore is unique. M. abscessus is the commonest NTM isolated, with a higher prevalence in males, and in the elderly. High NTM prevalence is associated with high rates of prior PTB in our cohort.

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.

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.

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.

Diagnostic performance of convex probe EBUS-TBNA in patients with mediastinal and coexistent endobronchial or peripheral lesions.

To compare the performance of convex probe endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) with conventional endobronchial biopsy (EBB) or transbronchial lung biopsy (TBLB) in patients with mediastinal, and coexisting endobronchial or peripheral lesions.Retrospective review of records of patients undergoing diagnostic EBUS-TBNA and conventional bronchoscopy in 2014.A total of 74 patients had mediastinal, and coexisting endobronchial or peripheral lesions. The detection rate of EBUS-TBNA for mediastinal lesion >1 cm in short axis, EBB for visible exophytic type of endobronchial lesion, and TBLB for peripheral lesion with bronchus sign were 71%, 75%, and 86%, respectively. In contrast, the detection rate of EBUS-TBNA for mediastinal lesion ≤1 cm in short axis, EBB for mucosal hyperemia type of endobronchial lesion, and TBLB for peripheral lesion without bronchus sign were 25%, 63%, and 38%, and improved to 63%, 88%, and 62% respectively by adding EBB or TBLB to EBUS-TBNA, and EBUS-TBNA to EBB or TBLB. Postprocedure bleeding was significantly more common in patients undergoing EBB and TBLB 8 (40%) versus convex probe EBUS-TBNA 2 patients (2.7%, P = 0.0004).EBUS-TBNA is a safer single diagnostic technique compared with EBB or TBLB in patients with mediastinal lesion of >1 cm in size, and coexisting exophytic type of endobronchial lesion, or peripheral lesion with bronchus sign. However, it requires combining with EBB or TBLB and vice versa to optimize yield when mediastinal lesion is ≤1 cm in size, and coexisting endobronchial and peripheral lesions lack exophytic nature, and bronchus sign, respectively.

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

To 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.

Evaluation of pulmonary nodules in Asian population.

BACKGROUND: American College of Chest Physicians (ACCP) provides guidelines to manage pulmonary nodules. Pulmonary nodules however can be malignant or benign. Similar incidence of tuberculosis (TB) and lung cancer in Asian countries raises concern over the relevance of suggested guidelines in Asian population. There is little data on the pattern of clinical practice in the management of pulmonary nodules in Asian country (Singapore). Our study describes the current pattern of clinical practice in this area highlighting the variation in practice and discussing the potential reasons. METHODS: Retrospective review of the medical records of patients diagnosed with lung cancer in 2010. RESULTS: Sixty nodules were identified in 32 patients. Nodules were detected incidentally on routine imaging in 7 (21.9%) patients. TB contact tracing and pre-employment screening were common ways by which nodules were detected incidentally. Over one third (37.5%) were non-smokers. Majority of nodules were located in the upper lobes of right and left lung followed by right lower lobe (RLL). Only few patients 8 (25%) had positron emission tomography (PET) scan for staging purposes. There were no difference in survival between patients who presented with single, 747 (range, 25-1,840) days vs. multiple nodules 928 (range, 30-2,572) days, P=0.26. In a retrospective analysis of malignancy risk with the probability calculator, 62.5% patients were at low-moderate risk whilst 32.5% were at high risk. CONCLUSIONS: The clinical practice of managing pulmonary nodules in Asian population differs from ACCP guidelines. None of the patient had pre-test probability calculated, and few had PET scan. This is because upper lobe predominance of lung cancer is identical to TB, non-smoking history does not have any weight in discounting malignancy risk where many of the Asian lung cancer patients are non-smokers, and the local endemicity of TB and its confounding effect on radiological findings of CT scan and PET scan.

Can EGFR-Tyrosine Kinase Inhibitors (TKI) Alone Without Talc Pleurodesis Prevent Recurrence of Malignant Pleural Effusion (MPE) in Lung Adenocarcinoma.

BACKGROUND AND OBJECTIVE: Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) are effective against lung adenocarcinoma. However, limited data is available assessing the effectiveness of EGFR-TKI use in preventing re-accumulation of MPE. To our knowledge, there is no literature on comparison of talc pleurodesis with EGFR-TKIs alone on re-accumulation of MPE in Asian population. We investigated if EGFR-TKI therapy for advanced lung adenocarcinoma with malignant pleural effusion (MPE) is also successful in preventing pleural fluid re-accumulation following initial drainage. METHODS: An observational cohort study of patients with lung adenocarcinoma and MPE in the year 2012 was conducted. RESULTS: 70 patients presented with MPE from lung adenocarcinoma. Fifty six underwent EGFR mutation testing of which 39 (69.6%) had activating EGFR mutation and 34 (87.1%) received TKI. 20 were managed by pleural fluid drainage only whereas 14 underwent talc pleurodesis following pleural fluid drainage. Time taken for the pleural effusion to re-accumulate in those with and without pleurodesis was 9.9 vs. 11.7 months, p=0.59 respectively. More patients (n=10, 25.6%) with activating EGFR mutation presented with complete opacification (white-out) of the hemithorax compared to none without activating EGFR mutation (p=0.02). CONCLUSION: In TKI eligible patients, early talc pleurodesis may not confer additional benefit in preventing re-accumulation of pleural effusion and may be reserved for non-adenocarcinoma histology, or EGFR negative adenocarcinoma. Complete opacification of the hemithorax on presentation may serve as an early radiographic signal of positive EGFR mutation status.

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.

Timeliness of Diagnosing Lung Cancer: Number of Procedures and Time Needed to Establish Diagnosis: Being Right the First Time.

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.

Vitamin E Isoform γ-Tocotrienol Downregulates House Dust Mite-Induced Asthma.

Inflammation and oxidative damage contribute to the pathogenesis of asthma. Although corticosteroid is the first-line treatment for asthma, a subset of patients is steroid resistant, and chronic steroid use causes side effects. Because vitamin E isoform γ-tocotrienol possesses both antioxidative and anti-inflammatory properties, we sought to determine protective effects of γ-tocotrienol in a house dust mite (HDM) experimental asthma model. BALB/c mice were sensitized and challenged with HDM. Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts, oxidative damage biomarkers, and cytokine levels. Lungs were examined for cell infiltration and mucus hypersecretion, as well as the expression of antioxidants and proinflammatory biomarkers. Sera were assayed for IgE and γ-tocotrienol levels. Airway hyperresponsiveness in response to methacholine was measured. γ-Tocotrienol displayed better free radical-neutralizing activity in vitro and inhibition of BAL fluid total, eosinophil, and neutrophil counts in HDM mouse asthma in vivo, as compared with other vitamin E isoforms, including α-tocopherol. Besides, γ-tocotrienol abated HDM-induced elevation of BAL fluid cytokine and chemokine levels, total reactive oxygen species and oxidative damage biomarker levels, and of serum IgE levels, but it promoted lung-endogenous antioxidant activities. Mechanistically, γ-tocotrienol was found to block nuclear NF-κB level and enhance nuclear Nrf2 levels in lung lysates to greater extents than did α-tocopherol and prednisolone. More importantly, γ-tocotrienol markedly suppressed methacholine-induced airway hyperresponsiveness in experimental asthma. To our knowledge, we have shown for the first time the protective actions of vitamin E isoform γ-tocotrienol in allergic asthma.

Subconjunctival haemorrhage from bronchoscopy: A case report.

Flexible bronchoscopy has been available for almost five decades. It has evolved as one of the most commonly used invasive diagnostic and therapeutic procedure in pulmonology, and its scope of applications is progressively expanding with the addition of new adjunct technologies such as endobronchial ultrasound, bronchial Thermoplasty, and navigational bronchoscopy. It is a safe procedure with complications ranging from fever, infiltrates, hypoxemia, bleeding, pneumothoraces and death, with most significant complications being bleeding and pneumothorax. We report a case of subconjuctival haemorrhage as an immediate complication of bronchoscopy. To our knowledge this is the first report documenting this rare complication.

Bilateral fractured neck of the femur in an adult patient with cystic fibrosis.

A 34-year-old man with cystic fibrosis (CF) sustained a bilateral fractured neck of the femur during the course of six grand mal seizures. The fractures were successfully treated with bipolar hemi-arthroplasties. Several risk factors for osteoporosis were present. Bone pathology showed reduced femoral head bone density. Osteoporosis of the lumbar spine was confirmed by dual-energy X-ray absorptiometry. As the life expectancy of patients with CF continues to improve, osteoporosis and its sequelae will become more common. We should be aware of the increased risk of bilateral fractured neck of the femur following epileptic seizure in CF.

Early discharge and home supervision of patients with pulmonary embolism treated with low-molecular weight heparin.

BACKGROUND: The objective of the study is to determine the efficacy, safety and feasibility of home treatment with low-molecular weight heparin (LMWH) in patients with symptomatic pulmonary embolism (PE). METHODS: All patients with PE on the home treatment programme between January 1998 and December 1999 were identified. Age, sex, length of hospital stay, risk factors for PE, ventilation perfusion (V/Q) lung scanning results, baseline investigations and treatment regimen were recorded. PE was defined as a clinical diagnosis supported by a high, intermediate or low probability V/Q lung scan. The efficacy of the treatment is defined as the event rate of recurrent PE. The safety outcome is defined as the rate of haemorrhage and the mortality that was related to the treatment during the 6-month follow-up period. RESULTS: Seventy patients were identified. Of these, 68 were hospitalised initially with a mean+/-S.D. length of hospital stay of 4.0+/-3.3 (range 0-17) days; their mean+/-S.D. age was 54.6+/-20.5 (range 19-87) years. Cardiopulmonary disease was the commonest pre-existing condition and 86% patients had at least one risk factor. All except one was haemodynamically stable. During the 6 months after discharge, 20 patients (28.6%) were readmitted at least once. One patient (1.4%) had symptomatic recurrent PE, one (1.4%) had haemoptysis and the remainder had unrelated pathology. There were no episodes of serious haemorrhage, and the two deaths that occurred in this period were not due to further PE. CONCLUSION: Early discharge home for stable patients with PE treated with LMWH (tinzaparin) is feasible, effective and safe, provided that patients are clinically stable, accessible by phone, receive daily administration of LMWH and have their international normalised ratio (INR) monitored.