Procalcitonin and antibiotics in moderate-severe acute exacerbation of chronic obstructive pulmonary disease: to use or not to use.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Acute exacerbations of COPD (AECOPD) are major driver for healthcare utilization with each exacerbation begetting the next exacerbation. It is, therefore, important to treat each episode effectively to prevent the next. However, this can be challenging as AECOPD result from complex interactions between host, environment and infective agents. The benefits of starting antibiotics in AECOPD, which are not life-threatening (e.g. not requiring mechanical ventilation) or not complicated by pneumonia remain controversial. RECENT FINDINGS: The use of procalcitonin to guide antibiotic therapy in AECOPD has gained interest in recent years. The main advantage of this approach is a safe reduction in antibiotic use in a large group of patients, which may potentially translate to several other benefits. These include reduced antibiotic-related side-effects, reduced risk of developing antibiotic-resistant organisms and cost savings. This approach is associated with no increase in mortality or morbidity such as treatment failure, re-admission, admission to ICU. SUMMARY: Procalcitonin-guided antibiotic therapy in AECOPD is a promising and safe approach, which may be ready for the prime time.

Ministry of Health Clinical Practice Guidelines: Chronic Obstructive Pulmonary Disease.

The Ministry of Health (MOH) has updated the Clinical Practice Guidelines on Chronic Obstructive Pulmonary Disease (COPD) to provide doctors and patients in Singapore with evidence-based treatment for COPD. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH Clinical Practice Guidelines on COPD, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: https://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Trigger factors in asthma and chronic obstructive pulmonary disease: a single-centre cross-sectional survey.

INTRODUCTION: The presence of trigger factors may help to distinguish asthma from chronic obstructive pulmonary disease (COPD). Knowing and avoiding trigger factors for both asthma and COPD can facilitate the design of comprehensive management programmes that can aid disease control. This study aimed to describe the relative frequency and range of various trigger factors in asthma and COPD. METHODS: We conducted a telephone-based survey involving asthma and COPD patients on follow-up at a university hospital in Singapore. RESULTS: A total of 779 asthma patients and 129 COPD patients participated in this study. Among these patients, 93.8% of those with asthma and 42.6% of those with COPD had trigger factors (p < 0.001). The median number of trigger factors was greater among asthma patients than among those with COPD (3 vs. 0, p < 0.001). Trigger factors found to be significantly more prevalent among asthma patients compared to those with COPD include tobacco smoke, alcohol, upper respiratory tract infections, incense smoke, perfume, laughter, a dusty environment, air-conditioning, heavy rain, heavy traffic fumes, citrus fruits, gastro-oesophageal reflux, household pets, flowers/pollen, medications and psychological triggers. Trigger factors that were not previously described, such as bathing, fatigue, insufficient sleep, crowded places and overeating, were also reported. CONCLUSION: Trigger factors, although found in both groups of patients, were more common among asthma patients. Knowledge of these trigger factors may be useful in distinguishing between the two diseases and optimising disease management.

Psychiatric comorbidities in Asian adolescent asthma patients and the contributions of neuroticism and perceived stress.

PURPOSE: Psychiatric comorbidity is reported to be common among adolescents with asthma, but little is known about its underlying psychological factors. OBJECTIVE: This study explored the profile of anxiety and depressive comorbidities among adolescents with well-controlled and poorly controlled asthma and the contribution of neuroticism and perceived stress. METHODS: The Revised Child Anxiety and Depression Scale, Neuroticism subscale of Big Five Inventory, Perceived Stress Scale, and Asthma Control Test were administered to 198 adolescents (aged 12-19 years) with well-controlled (n = 137) and poorly controlled asthma (n = 61) as well as 171 healthy neighborhood controls. RESULTS: Adolescents with poorly controlled asthma, compared with well-controlled asthma patients and healthy controls, had higher scores of depression (p = .006), panic attacks (p = .002), total anxiety (p = .038), and total internalizing symptoms (p = .017), after adjusting for gender, age, ethnicity, smoking status, and family housing type. Adolescents with asthma had higher neuroticism (p = .025), perceived stress (p = .022), and body mass index (p = .006) and lower self-rated health (p < .001) than healthy controls. No significant differences in psychiatric comorbidity scores were observed after accounting for differences in underlying psychological and physical factors. Among asthma patients, increased asthma control was associated with decreased scores of psychiatric comorbidity (p < .01), but the association was not significant after allowing for decreased neuroticism and perceived stress. CONCLUSIONS: The diagnosis of asthma and poor asthma control in adolescents is associated with excess psychiatric comorbidity, which is likely due to increased neuroticism and perceived stress.

Impact of a palliative care initiative on end-of-life care in the general wards: a before-and-after study.

BACKGROUND: Data on deaths in the general wards of our hospital in 2007 revealed infrequent discussions on end-of-life care and excessive burdensome interventions. AIM: A physician order form to withhold inappropriate life-sustaining interventions was initiated in 2009. The use of the form was facilitated by staff educational sessions and a palliative care consult service. This study aims to evaluate the impact of these interventions in 2010. DESIGN: Retrospective medical chart review with comparisons was made for the following: baseline patient characteristics, orders concerning life-sustaining therapies, treatment provided in last 24 h of life, and discussion of specific life-sustaining therapies with patients and families. SETTINGS/PARTICIPANTS: This study included all adult patients who died in our hospital's general wards in 2007 (N = 683) versus 2010 (N = 714). RESULTS: There was an increase in orders to withhold life-sustaining therapies, such as cardiopulmonary resuscitation (66.2%-80.0%). There was a decrease in burdensome interventions such as antibiotics (44.9%-24.9%) and a small increase in palliative treatments such as analgesia (29.1%-36.7%). There were more discussions on the role of cardiopulmonary resuscitation with conversant patients (4.6%-10.2%) and families (56.5%-79.8%) (p-value all < 0.05). On multivariate analysis, the physician order form independently predicted orders to withhold cardiopulmonary resuscitation. CONCLUSIONS: A multifaceted intervention of a physician order form, educational sessions, and palliative care consult service led to an improvement in documentation of end-of-life discussions and was associated with an increase in such discussions and less burdensome treatments. There were small improvements in the proportion of palliative treatments administered.

Predicting mortality among older adults hospitalized for community-acquired pneumonia: an enhanced confusion, urea, respiratory rate and blood pressure score compared with pneumonia severity index.

BACKGROUND AND OBJECTIVE: Pneumonia Severity Index (PSI) predicts mortality better than Confusion, Urea >7 mmol/L, Respiratory rate >30/min, low Blood pressure: diastolic blood pressure <60 mm Hg or systolic blood pressure <90 mm Hg, and age >65 years (CURB-65) for community-acquired pneumonia (CAP) but is more cumbersome. The objective was to determine whether CURB enhanced with a small number of additional variables can predict mortality with at least the same accuracy as PSI. METHODS: Retrospective review of medical records and administrative data of adults aged 55 years or older hospitalized for CAP over 1 year from three hospitals. RESULTS: For 1052 hospital admissions of unique patients, 30-day mortality was 17.2%. PSI class and CURB-65 predicted 30-day mortality with area under curve (AUC) of 0.77 (95% confidence interval (CI): 0.73-0.80) and 0.70 (95% CI: 0.66-0.74) respectively. When age and three co-morbid conditions (metastatic cancer, solid tumours without metastases and stroke) were added to CURB, the AUC improved to 0.80 (95% CI: 0.77-0.83). Bootstrap validation obtained an AUC estimate of 0.78, indicating negligible overfitting of the model. Based on this model, a clinical score (enhanced CURB score) was developed that had possible values from 5 to 25. Its AUC was 0.79 (95% CI: 0.76-0.83) and remained similar to that of PSI class. CONCLUSIONS: An enhanced CURB score predicted 30-day mortality with at least the same accuracy as PSI class did among older adults hospitalized for CAP. External validation of this score in other populations is the next step to determine whether it can be used more widely.

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.

End-of-life care in the general wards of a Singaporean hospital: an Asian perspective.

BACKGROUND: Despite international differences in cultural perspectives on end-of-life issues, little is known of the care for the dying in the general wards of acute hospitals in Asia. METHODS: We performed a retrospective medical chart review of all 683 adult patients who died without intensive care unit (ICU) admission in our Singaporean hospital in 2007. We first evaluated the prevalence of do-not-resuscitate (DNR) orders and orders for or against life-sustaining therapies; second, if such orders were discussed with the patients and/or family members; and third, the actual treatments provided before death. RESULTS: There were DNR orders for 66.2% of patients and neither commitment for DNR nor cardiopulmonary resuscitation (CPR) for 28.1%. Orders to limit life-sustaining therapies, including ICU admission, intubation, and vasopressors/inotropes were infrequent. Only 6.2% of the alert and conversant patients with DNR orders were involved in discussions on these orders. In contrast, such discussions with their family members occurred 82.9% of the time. Interventions in the last 24 hours of life included CPR (9.4%), intubation (6.4%), vasopressors/inotropes (14.8%), tube feeding (24.7%), and antibiotics (44.9%). Analgesia was provided in 29.1% of patients. CONCLUSIONS: There was a lack of commitment by doctors on orders for DNR/CPR and to limit life-sustaining therapies, infrequent discussions with patients on end-of-life decisions, and excessive burdensome interventions with inadequate palliative care for the dying. These findings may reflect certain Asian cultural biases. More work is required to improve our quality of end-of-life care.

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.

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.

Noninvasive and invasive ventilation in acute respiratory failure associated with bronchiectasis.

PURPOSE: To describe the outcomes of patients with bronchiectasis and acute respiratory failure (ARF) treated with noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) after a failure of conservative measures, and to identify the predictors of hospital mortality and NIV failure. METHODS: Retrospective review of bronchiectatic patients on NIV (n = 31) or IMV (n = 26) for ARF over 8 years in a medical intensive care unit (ICU) experienced in NIV. RESULTS: At baseline, the NIV group had more patients with acute exacerbations without identified precipitating factors (87.1 vs. 34.6%, p < 0.001), higher pH (mean 7.25 vs. 7.18, p = 0.008) and PaO(2)/FiO(2) ratio (mean 249.4 vs. 173.2, p = 0.02), and a trend towards a lower APACHE II score (mean 25.3 vs. 28.4, p = 0.07) than the IMV group. There was no difference in hospital mortality between the two groups (25.8 vs. 26.9%, p > 0.05). The NIV failure rate (need for intubation or death in the ICU) was 32.3%. Using logistic regression, the APACHE II score was the only predictor of hospital mortality (OR 1.19 per point), and the PaO(2)/FiO(2) ratio was the only predictor of NIV failure (OR 1.02 per mmHg decrease). CONCLUSIONS: The hospital mortality of patients with bronchiectasis and ARF approximates 25% and is predicted by the APACHE II score. When selectively applied, NIV fails in one-third of the patients, and this is predicted by hypoxemia. Our findings call for randomised controlled trials to compare NIV versus IMV in such patients.

First endoscopic procedure for diagnosis and staging of mediastinal lymphadenopathy.

AIM: To compare a first diagnostic procedure of transbronchial needle aspiration (TBNA) with selection of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or TBNA for mediastinal lymphadenopathy. METHODS: Sixty-eight consecutive patients with mediastinal lymphadenopathy on computed tomography (CT), who required cytopathological diagnosis, were recruited. The first 34 underwent a sequential approach in which TBNA was performed first, followed by EUS-FNA if TBNA was unrevealing. The next 34 underwent a selective approach where either TBNA or EUS-FNA was selected as the first procedure based on the CT findings. RESULTS: The diagnostic yield of TBNA as the first diagnostic procedure in the sequential approach was 62%. In the selective approach, the diagnostic yield of the first procedure was 71%. There was no significant difference in the overall diagnostic yield, but there were significantly fewer combined procedures with the selective approach. CONCLUSION: Selecting either EUS-FNA or TBNA as the first diagnostic procedure achieved a comparable diagnostic yield with significantly fewer procedures than performing TBNA first in all patients.

Factors associated with acute health care use in a national adult asthma management program.

BACKGROUND: The use of acute health care resources for asthma is considerable. Disease severity is an established risk factor, but ethnicity and health care factors are less well studied. OBJECTIVE: To investigate the independent associations of ethnicity and health care factors with acute resource use for asthma. METHODS: Longitudinal data from a national adult asthma management program providing universal access to care were analyzed. Outcome measures were unscheduled physician visits with urgent nebulization, emergency department (ED) visits, and hospitalizations. RESULTS: In multivariate analyses, markers of disease severity were found to be significantly associated with all acute resource use. After controlling for disease severity, ethnicity was associated with increased risk of all acute resource use; Indian (vs Chinese) ethnicity was associated with increased risk of unscheduled physician visits (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.03-1.70), ED visits (HR, 1.61; 95% CI, 1.12-2.32), and hospitalizations (HR, 1.49; 95% CI, 1.03-2.16). Malay ethnicity was associated with unscheduled physician visits (HR, 1.30; 95% CI, 1.01-1.68) and ED visits (HR, 1.55; 95% CI, 1.09-2.19). Default of follow-up appointments was associated with unscheduled physician visits (HR, 1.47; 95% CI, 1.08-2.00), ED visits (HR, 2.35; 95% CI, 1.59-3.45), and hospitalizations (HR, 1.74; 95% CI, 1.09-2.76). Poor inhaler technique was associated with ED visits (HR, 1.86; 95% CI, 1.05-3.30) and smoking with unscheduled physician visits (HR, 1.38; 95% CI, 1.09-1.76). CONCLUSIONS: In addition to markers of asthma severity, ethnicity, smoking, discontinuity of care, and self-care behavior are risk factors for acute resource utilization and represent target groups and elements of asthma intervention for improving asthma outcomes.