Role of pneumococcal vaccination in prevention of pneumococcal disease among adults in Singapore.

The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults.

Insights, attitudes and perceptions about asthma and its treatment: findings from a multinational survey of patients from 8 Asia-Pacific countries and Hong Kong.

BACKGROUND AND OBJECTIVE: The Asthma Insight and Management (AIM) survey was conducted in North America, Europe, the Asia-Pacific region and Latin America to characterize patients' insights, attitudes and perceptions about their asthma and its treatment. We report findings from the Asia-Pacific survey. METHODS: Asthma patients (≥12 years) from Australia, China, Hong Kong, India, Malaysia, Singapore, South Korea, Taiwan and Thailand were surveyed. Patients answered 53 questions exploring general health, diagnosis/history, symptoms, exacerbations, patient burden, disease management, medications/treatments and patient's attitudes. The Global Initiative for Asthma guidelines were used to assess asthma control. The survey was conducted by random digit telephone dialling (Australia, China and Hong Kong) or by random face-to-face interviews (India, Malaysia, Singapore, South Korea, Taiwan and Thailand). RESULTS: There were 80 761 households screened. Data from 3630 patients were collected. Wide disparity existed between objective measures of control and patient perception. Reported exacerbations during the previous year ranged from 19% (Hong Kong) to 67% (India). Reported unscheduled urgent/emergency visits to a doctor's office/hospital/clinic in the previous year ranged from 15% (Hong Kong) to 46% (Taiwan). Patients who reported having controlled asthma in the previous month ranged from 27% (South Korea) to 84% (Taiwan). Substantial functional and emotional limitations due to asthma were identified by 13% (South Korea) to 78% (India) of patients. CONCLUSIONS: Asthma has a profound impact on patients' well-being despite the availability of effective treatments and evidence-based management guidelines. Substantial differences across the surveyed countries exist, suggesting unmet, country-specific cultural and educational needs. A large proportion of asthma patients overestimate their level of control.

Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer.

There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

Female reproductive factors, gene polymorphisms in the estrogen metabolism pathway, and risk of lung cancer in Chinese women.

The authors examined relations between reproductive factors and 5 estrogen pathway gene polymorphisms (CYP17 rs743572, CYP19A1 rs10046, ERß rs1256049, ERß rs4986938, and COMT rs4680) among 702 Singapore Chinese female lung cancer cases and 1,578 hospital controls, of whom 433 cases (61.7%) and 1,375 controls (87.1%) were never smokers. Parity (per child, odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87, 0.97) and menstrual cycle length (for ≥30 days vs. <30 days, OR = 0.50, 95% CI: 0.32, 0.80) were inversely associated with lung cancer in never smokers, while age at first birth (for ages 21-25, 26-30, and ≥31 years vs. ≤20 years, ORs were 1.54, 2.17, and 1.30, respectively), age at menopause (for ages 49-51 and ≥52 years vs. ≤48 years, ORs were 1.37 and 1.59; P(trend) = 0.003), and reproductive period (for 31-33, 34-36, 37-39, and ≥40 years vs. ≤30 years, ORs were 1.06, 1.25, 1.45, and 1.47; P(trend) = 0.026) were positively associated. Among smokers, parity was inversely associated with lung cancer, but there was no association with other reproductive factors. The COMT rs4680 A allele was positively associated with lung cancer in never smokers (for G/A or A/A vs. G/G, OR = 1.46, 95% CI: 1.12, 1.90) but not in ever smokers. No associations were seen with other polymorphisms. These results support a risk-enhancing role of estrogens in lung carcinogenesis among never smokers.

Meat consumption and risk of lung cancer among never-smoking women.

The relationship between diet and lung cancer, apart from the protective effect of fruit and vegetables, is poorly understood. Reports on the role of dietary components such as meat are inconsistent, and few studies include sufficient numbers of nonsmokers. We examined the relationship between meat consumption and never-smoking lung cancer in a hospital-based case-control study of Singapore Chinese women, a population with low smoking prevalence. Three hundred and ninety-nine cases and 815 controls were recruited, of whom 258 cases and 712 controls were never smokers. A standardized questionnaire (which included a food frequency questionnaire module) was administered by trained interviewers. Among these never smokers, fruit and vegetable intake were inversely associated with lung cancer risk. Seventy-two percent of meat consumed was white meat (chicken or fish). Meat consumption overall was inversely associated with lung cancer [adjusted odds ratio (OR), 0.88, 0.59 for second, third tertiles, P (trend) = .012]. An inverse relationship between fish consumption and lung cancer (adjusted OR, 0.81, 0.47 for 2nd, 3rd tertiles, P (trend) < .001) was observed. No association was seen between consumption of processed meats and lung cancer, nor between dietary heterocyclic amines and lung cancer. Our data suggest that fish consumption may be protective against lung cancer in never smokers.

Pulmonary sclerosing hemangioma: pitfalls in management.

Pulmonary sclerosing hemangioma is a rare benign tumor for which surgical excision is curative with an excellent prognosis. It often mimics malignancy, making it a diagnostic and management challenge. We reviewed the clinical, radiological, and histopathological characteristics as well as the surgical management of our patients to assess the potential pitfalls in management. All 19 patients who underwent surgical biopsy between January 1999 and December 2009 with a final histopathological diagnosis of pulmonary sclerosing hemangioma were reviewed retrospectively. The median age was 48 years, 89.5% were female, 89.5% were Chinese, and 68.4% were asymptomatic. There were no specific diagnostic radiological characteristics; 1 of 3 patients who underwent combined positron-emission and computed tomography had a false-positive result. Preoperative attempts at establishing a diagnosis were successful in 20% of patients who had invasive procedures. Intraoperative frozen-section evaluation for pulmonary sclerosing hemangioma had an error rate of 25% and a deferred rate of 31%, resulting in nearly half of our patients undergoing unnecessary extensive surgical procedures. We hope to heighten awareness of this diagnosis, thereby increasing the index of suspicion and minimizing errors in diagnosis.

Polymorphisms in inflammatory pathway genes, host factors and lung cancer risk in Chinese female never-smokers.

Inflammation appears to be important in lung carcinogenesis among smokers, but its role among never-smokers is not well established. We hypothesized that inflammatory medical conditions and gene polymorphisms interact to increase lung cancer risk in never-smokers. We interviewed 433 Singaporean female never-smoker lung cancer patients and 1375 hospital controls, and evaluated six polymorphisms in the interleukin 1-ß, interleukin 6 (IL6), cyclooxygenase-2, peroxisome proliferator-activated receptor-γ and interleukin 1-ß receptor antagonist (IL1RN) genes. Tuberculosis was associated with a non-significant elevated risk of lung cancer [odds ratio (OR) 1.58, 95% confidence interval (CI) 0.95-2.62]. There was no effect of asthma, atopy or chronic productive cough individually. However, the presence of one or more of these conditions (asthma, cough or atopy) increased risk (OR 2.24, 95%CI 1.15-4.38) in individuals possessing the T/T genotype at interleukin 1-ß -31T/C, but not in those possessing the C/T (OR 0.87, 95%CI 0.51-1.57) or C/C genotypes (OR 0.58, 95%CI 0.27-1.27), and in individuals having the *2 variable number of tandem repeat allele of IL1RN [OR 5.09 (1.39-18.67)], but not in those without (OR 0.93, 95%CI 0.63-1.35). The IL6-634 G allele increased the risk of lung cancer (OR 1.44, 95%CI 1.07-1.94). Lung cancer risk also increased with the number of polymorphism sites where at least 1 'risk' allele was present [interleukin 1-ß -31T/C (T allele), IL1RN (*2 allele) and IL6-634C/G (G allele)] among those with asthma, cough or atopy (Ptrend 0.001) but not in those without (Ptrend 0.47). Our results suggest that the effect of inflammatory medical conditions on lung cancer in never-smokers is modulated by host genetic susceptibility and will need to be confirmed in other studies conducted in similar populations.

Lung cancer in Chinese women: evidence for an interaction between tobacco smoking and exposure to inhalants in the indoor environment.

BACKGROUND: Epidemiologic data suggest that Chinese women have a high incidence of lung cancer in relation to their smoking prevalence. In addition to active tobacco smoke exposure, other sources of fumes and airborne particles in the indoor environment, such as cooking and burning of incense and mosquito coils, have been considered potential risk factors for lung cancer. OBJECTIVES: We used a case-control study to explore effects of inhalants from combustion sources common in the domestic environment on lung cancer and their modification by active tobacco smoking. METHODS: We analyzed 703 primary lung cancer cases and 1,578 controls. Data on demographic background and relevant exposures were obtained by face-to-face interviews in the hospital. RESULTS: We observed a positive relationship with daily exposure to incense or mosquito coils and to cooking fumes only among smokers, and no association among lifetime nonsmokers. Interactions between smoking and frequency of cooking, or exposure to incense or mosquito coils were statistically significant and consistent with synergistic effects on lung cancer. The odds ratio (OR) comparing smokers without daily incense or mosquito coil exposure with nonsmokers without daily exposure was 2.80 [95% confidence interval (CI), 1.86-4.21], whereas the OR comparing smokers with daily exposure to the same referent group was 4.61 (95% CI, 3.41-6.24). In contrast, daily exposure to incense or mosquito coils was not associated with lung cancer among nonsmokers (OR = 0.91; 95% CI, 0.72-1.16). We observed the same pattern of associations for smokers without (OR = 2.31; 95% CI, 1.52-3.51) and with (OR = 4.50; 95% CI, 3.21-6.30) daily cooking exposure compared with nonsmokers, with no evidence of an association with daily cooking exposure among nonsmokers. CONCLUSION: Our results suggest that active tobacco smoking not only is an important risk factor for development of lung cancer, but also may cause smokers to be more susceptible to the risk-enhancing effects of other inhalants.

Primary tracheal lymphoma causing respiratory failure.

Lymphomatous involvement of the airway causing stridor is a rare but frightening presentation of an eminently treatable condition. We describe a 24-year-old woman with tracheal non-Hodgkin lymphoma who was initially diagnosed with asthma, but subsequently presented with near-fatal acute upper airway obstruction because of a tracheal Anaplastic Lymphoma Kinase (ALK)+ anaplastic T-cell lymphoma. The obstructing tumor was extricated by means of rigid bronchoscopy. After six cycles of Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone chemotherapy, the patient went into complete clinical remission. A high index of suspicion in patients with dyspnoea and wheeze unresponsive to bronchodilators is crucial in early diagnosis of tracheal tumors.

Induction concurrent chemoradiotherapy using Paclitaxel and Carboplatin combination followed by surgery in locoregionally advanced non-small cell lung cancer--Asian experience.

INTRODUCTION: It has been established that combined chemoradiotherapy treatment benefits selected patients with stage III Non Small Cell Lung Cancer (NSCLC). However, locoregional recurrence still poses a problem. The addition of surgery as the third modality may provide a possible solution. We report our experience of using the triple-modality approach in this group of patients. MATERIALS AND METHODS: This is a retrospective review of 33 patients with stage III NSCLC treated between 1997 and 2005. Patients have good performance status and no significant weight loss. There were 26 males (79 %) with median age of 63 years (range, 43 to 74) and median follow-up of 49 months. Seventy-six percent had Stage IIIA disease. Chemotherapy consisted of paclitaxel at 175 mg/m2 over 3 hours followed by carboplatin at AUC of 5 over 1 hour. Thoracic radiotherapy was given concurrently with the second and third cycles of chemotherapy. All patients received 50 Gray in 25 fractions over 5 weeks. RESULTS: The main toxicities were grade 3/4 neutropenia (30%), grade 3 infection (15 %) and grade 3 oesophagitis (9%). Twenty-five patients (76%) underwent surgery. Of the 8 who did not undergo surgery, 1 was deemed medically unfit after induction chemoradiotherapy and 4 had progressive disease; 3 declined surgery. Nineteen patients (58 %) had lobectomy and 6 had pneumonectomy. The median overall survival was 29.9 months and 12 patients are still in remission. CONCLUSION: The use of the triplemodality approach is feasible, with an acceptable tolerability and resectability rate in this group of patients.

Clinical application of airway bypass with paclitaxel-eluting stents: early results.

OBJECTIVE: To assess the safety and early clinical results of a multicenter evaluation of airway bypass with paclitaxel-eluting stents for selected patients with severe emphysema. METHODS: Airway bypass was performed with a fiberoptic bronchoscope in three steps: identification of a blood vessel-free location with a Doppler probe at the level of segmental bronchi, fenestration of the bronchial wall, and placement of a paclitaxel-eluting stent to expand and maintain the new passage between the airway and adjacent lung tissue. All adverse events were recorded, as well as 1- and 6-month pulmonary function tests and dyspnea index. RESULTS: Thirty-five patients received the airway bypass procedure with a median of 8 stents implanted per patient. At 1-month follow-up, statistically significant differences in residual volume, total lung capacity, forced vital capacity, forced expiratory volume, modified Medical Research Council scale, 6-minute walk, and St George's Respiratory Questionnaire were observed. At the 6-month follow-up, statistically significant improvements in residual volume and dyspnea were demonstrated. One death occurred after bleeding during the procedure. Retrospective analysis revealed that the degree of pretreatment hyperinflation may be an important indicator of which patients achieve the best short- and long-term results. CONCLUSIONS: The airway bypass procedure reduces hyperinflation and improves pulmonary function and dyspnea in selected patients with severe emphysema. Duration of benefit appears to correlate with the degree of pretreatment hyperinflation. These preliminary clinical results support further evaluation of the procedure.

Pulmonary capillaritis in IgA nephropathy.

Pulmonary capillaritis presenting as diffuse alveolar hemorrhage is a rare manifestation in patients with IgA nephropathy. A 20-year-old male with hemodialysis dependent, end-stage renal failure presented with recurrent hemoptysis and respiratory failure. A histologic diagnosis of pulmonary capillaritis was established by transbronchial lung biopsy. He was successfully treated with intravenous methylprednisone and plasma exchange followed by oral prednisone and cyclophosphamide. This report highlights the independent renal and pulmonary manifestations of IgA nephropathy and the management of the resultant diffuse alveolar hemorrhage with aggressive immunosuppression.

Sarcoidosis in Singapore: epidemiology, clinical presentation and ethnic differences.

BACKGROUND AND OBJECTIVES: The aim of this study is to better understand the epidemiological and clinical features of patients with sarcoidosis in Singapore and to ascertain if ethnic differences exist. METHODS: A review of hospital medical records from June 1998 to May 2004 to identify patients with sarcoidosis. RESULTS: There were 59 patients with sarcoidosis identified (19 Chinese, 29 Asian Indian and 11 Malay). The estimated annual incidence of sarcoidosis in Singapore was 0.56 per 100,000. There was a significant difference between the observed and expected disease frequency in Chinese (32.2% vs 78.7%) and Indians (49.2% vs 6.0%, P < 0.005). A bimodal distribution of age at diagnosis was seen with peaks in the 30-39 years and 50-59 years age groups; 38.9% of cases were over the age of 50. Chinese patients were more likely to be asymptomatic (57.9%, P = 0.015) and less likely to have impaired spirometry (P = 0.013). Pulmonary sarcoid presented largely as stage 0 or stage 1 disease (74.4%). Overall mean spirometry was unimpaired and prognosis was good with 79.2% showing no radiological deterioration. There were no significant differences in organ involvement or treatment between ethnic groups. CONCLUSION: Sarcoidosis in Singapore is rare and the incidence differs between ethnic groups. Chinese appear to have a lower incidence and a less symptomatic presentation; Indians have a higher incidence and poorer clinical course.

Survival of small-cell lung cancer and its determinants of outcome in Singapore.

INTRODUCTION: The survival and epidemiology of small-cell lung cancer (SCLC) in Singapore has not been described. We aim to present the characteristics as well as determine the survival outcome and important prognostic factors for SCLC patients. MATERIALS AND METHODS: A retrospective analysis of SCLC patients diagnosed from 1999 to 2002 was conducted at the Outram campus, Singapore. Clinical characteristics and treatment data were obtained from case records and survival data were checked with the registry of births and deaths on 30 May 2005. RESULTS: One hundred and eleven patients were analysed. There were 38 (34.2%) limited-disease (LD) patients and 73 (65.8%) extensive-disease (ED) patients. The majority were current or former smokers (94.7% among LD and 94.5% among ED). More patients with LD had good performance status (92% versus 63%, P = 0.0003) and were treated with combined chemotherapy and radiotherapy (82% versus 48%, P = 0.012). The median survival time of LD patients treated with curative chemoradiotherapy was 14.2 months (95% CI, 10.96 to 17.44). Those given prophylactic cranial irradiation had a median survival time of 16.9 months (95% CI, 11.83 to 21.97). For ED patients, the median survival time was 8.17 months (95%CI, 5.44 to 10.89). None of the factors analysed were significant prognostic factors for LD patients while performance status and type of treatment given were significant among ED patients. CONCLUSIONS: We found that the characteristics and survival of SCLC patients in Singapore are fairly similar to that of other countries.

Endobronchial ultrasound for detection of tracheomalacia from chronic compression by vascular ring.

A 67-year-old female chronic smoker was evaluated for an asymptomatic right paratracheal mass and the diagnosis of double-arch aorta was made. She returned 2 years later with dyspnoea on exertion, productive cough and wheeze on lying supine. Flow volume curve showed variable intrathoracic airway obstruction, and bronchoscopy revealed extrinsic compression of the trachea by double-arch aorta with destruction of the cartilaginous layer visualized on endobronchial ultrasonography. Endobronchial ultrasonography may be a useful adjunctive tool for the identification of adults at risk of postoperative tracheomalacia where tracheopexy or airway stenting can be performed concurrently or sequentially if surgery is contemplated.

Differences between small-cell lung cancer and non-small-cell lung cancer among tobacco smokers.

It is known that smoking increases the risk for all histological subtypes of lung cancer. To date, the factors that determine why some patients develop small-cell lung cancer (SCLC) while others develop non-small-cell lung cancer (NSCLC) remain unknown. We compared the characteristics of 774 smokers with SCLC and NSCLC diagnosed during the period January 1999 till December 2002. Multivariate logistic regression was used to estimate the odds ratio (OR) with 95% CI. Testing of linear trend across categories of pack-years was also conducted. Six hundred and sixty-five NSCLC were compared to 109 SCLC. Among SCLC, there were significantly more females (20.2% versus 12.8%), current-smokers (81.7% versus 71.9%) as well as smokers who had smoked more than 40 pack-years (75.6% versus 50.3%). Comparing SCLC with NSCLC among the men only, having smoked more than 40 pack-years was associated with a significantly elevated odds ratio (OR) of 3.71 of developing SCLC (95% CI, 1.05-13.1; p=0.041). There was a decreasing trend in OR with increasing smoking cessation period. When comparing SCLC with adenocarcinoma, the women had a higher OR of 2.37 of developing SCLC (95% CI, 1.05-5.31; p=0.037) compared to the men. Our findings suggest that cumulative smoking exposure in terms of pack-years smoked is an important determining factor for the preferred development of SCLC among smokers.

Depressive symptoms and chronic obstructive pulmonary disease: effect on mortality, hospital readmission, symptom burden, functional status, and quality of life.

BACKGROUND: Depressive symptoms are common among patients with chronic obstructive pulmonary disease (COPD), but depression's impact on COPD outcomes has not been fully investigated. We evaluated the impact of comorbid depression on mortality, hospital readmission, smoking behavior, respiratory symptom burden, and physical and social functioning in patients with COPD. METHODS: In this prospective cohort study, 376 consecutive patients with COPD hospitalized for acute exacerbation were followed up for 1 year. The independent associations of baseline comorbid depression (designated as a Hospital Anxiety and Depression Scale score of > or =8) with mortality, hospital readmission, length of stay, persistent smoking, and quality of life (determined by responses to the St George Respiratory Questionnaire) were evaluated after adjusting for potential confounders. RESULTS: The prevalence of depression at admission was 44.4%. The median follow-up duration was 369 days, during which 57 patients (15.2%) died, and 202 (53.7%) were readmitted at least once. Multivariate analyses showed that depression was significantly associated with mortality (hazard ratio, 1.93; 95% confidence interval, 1.04-3.58), longer index stay (mean, 1.1 more days; P = .02) and total stay (mean, 3.0 more days; P = .047), persistent smoking at 6 months (odds ratio, 2.30; 95% confidence interval, 1.17-4.52), and 12% to 37% worse symptoms, activities, and impact subscale scores and total score on the St George Respiratory Questionnaire at the index hospitalization and 1 year later, even after controlling for chronicity and severity of COPD, comorbidities, and behavioral, psychosocial, and socioeconomic variables. CONCLUSIONS: Comorbid depressive symptoms in patients with COPD are associated with poorer survival, longer hospitalization stay, persistent smoking, increased symptom burden, and poorer physical and social functioning. Interventions that reduce depressive symptoms may potentially affect COPD outcomes.

Asthma fatalities at the Emergency Department of the Singapore General Hospital.

BACKGROUND: Bronchial asthma is one of the most common chronic diseases in Singapore and the prevalence is increasing. Despite this, the worldwide mortality rate from asthma has been noted to be low at an average of 2.0 per 100,000 people in developed countries such as the United States. Risk factors for fatal asthma attacks that have been described include excessive use of short acting beta-agonists, errors in clinical judgement, poor compliance, psychosocial disorders, use of three or more groups of asthma medication and indicators of asthma severity. AIM: We aim to study the incidence of asthma deaths occurring in the emergency department of a tertiary care hospital in Singapore. METHODS: Of the total number of patients at the Department of Emergency Medicine in Singapore General Hospital from January 1999 to June 2005, eight fatalities were attributed to exacerbation of bronchial asthma. The characteristics of these patients are described. RESULTS: A low incidence of asthma-related deaths is found in Singapore.