Circadian-rhythm differences among emergency department patients with chronic obstructive pulmonary disease exacerbation

The purpose of the study was determine whether patients with chronic obstructive pulmonary disease (COPD) exacerbation who present to the emergency department (ED) during the night (00:00 to 07:59 h) vs. other times of the day have more severe COPD exacerbation, require more intensive treatment, and have worse clinical outcomes. A multicenter cohort study was completed involving 29 EDs in the United States and Canada. Using a standard protocol, consecutive ED patients with COPD exacerbation were interviewed, and their charts were reviewed. Of 582 patients enrolled, 52% were women, and the median age was 71 yrs (interquartile range, 64-77 yrs). Nighttime patients (15% of cohort) did not differ from patients presenting at other times except that they were less likely to have private insurance, more likely to have a history of corticosteroid use, and have a shorter duration of symptoms exacerbation. Except for a few features indicative of more severe COPD exacerbation (such as higher respiratory rate at ED presentation, greater likelihood of receiving noninvasive positive pressure ventilation, and increased risk of endotracheal intubation), nighttime patients did not differ from other patients with respect to ED management. Nighttime patients were approximately three-fold more likely to be intubated in the ED (odds ratio, 3.46; 95% confidence interval, 1.10-10.9). There were no day-night differences regarding ED disposition and post-ED relapse. Except for some features indicating more severe exacerbation, nighttime ED patients had similar chronic COPD characteristics, received similar treatments in the ED, and had similar clinical outcomes compared with patients presenting to the ED at other times of the day.     

Prevalence and risk of viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease: a meta-analysis

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to substantial morbidity and mortality. Viral infections could be an important cause of acute exacerbations of COPD (AECOPD) and only a few studies report the prevalence of respiratory viruses on this disease. We aimed to update the review on the prevalence of respiratory viral infection in patients with AECOPD with a meta-analysis. We reviewed the prevalence of respiratory viruses on this disease by searching PubMed systematically to identify primary studies published from Jan 1990 to March 2012. Studies met with seven criteria were extracted for meta-analysis. A total of 17 studies were eligible for the meta-analysis. Weighted overall prevalence of respiratory viruses in patients with AECOPD was 39.3 % (95 % CI 36.9–41.6) with a high degree of a heterogeneity (I ² > 75 %). In contrast, the rate in stable COPD patients from four studies was 13.6 % (95 % CI 9.0–18.2) without any apparent heterogeneity. Pooled risk ratio for respiratory viral infection was 4.1 (95 % CI 2.0–8.5) for AECOPD as compared with stable COPD. Rhinovirus was the most common virus and with a weighted prevalence of 14.8 % (95 % CI 13.3–16.5). Respiratory viruses probably are important etiological agents in patients with AECOPD as compared with the stable COPD patients. This result would help to provide better strategies for management of AECOPD and health-care planning.     

急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物和病情严重程度的相关性CSCD

目的 探讨急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物、病情严重程度的相关性。方法 选择2018年3月至2019年9月我院收治的122例急性加重期慢性阻塞性肺疾病患者,根据其痰色评分分为1~2分组(n=30)与3~4分组(n=92),比较两组患者肺部微生物分布、病情严重程度分布、慢性阻塞性肺疾病评估测试(CAT)评分、白细胞(WBC)水平、C反应蛋白(CRP)水平,分析急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物、病情严重程度的相关性。结果 3~4分组患者肺部肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌、草绿色链球菌、白假丝酵母、酵母样真菌、丝状真菌检出率与1~2分组比较差异无统计学意义(均P>0.05)。3~4分组患者鲍曼不动杆菌检出率显著高于1~2分组(P<0.05)。3~4分组患者病情严重程度分布与1~2分组比较差异有统计学意义(P<0.05)。3~4分组患者CAT评分、WBC水平、CRP水平均显著高于1~2分组(均P<0.05)。急性加重期慢性阻塞性肺疾病患者痰色评分与肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌、草绿色链球菌、白假丝酵母、酵母样真菌、丝状真菌检出率无显著相关性(均P>0.05),而与鲍曼不动杆菌检出率、CAT评分、WBC水平、CRP水平、病情严重程度呈显著相关性(均P<0.05)。结论 痰色评分与急性加重期慢性阻塞性肺疾病患者肺部微生物和病情严重程度关系密切,有望成为临床评价该类患者肺部微生物分布及病情严重程度的方法之一。     

Patients with acute exacerbation of chronic obstructive pulmonary disease feel safe when treated at home: a qualitative study

ABSTRACT: BACKGROUND: The design of new interventions to improve health care for patients with chronic obstructive pulmonary disease (COPD) requires knowledge about what patients with an acute exacerbation experience as important and useful. The objective of the study was to explore patients' experiences of an early discharge hospital at home (HaH) treatment programme for exacerbations in COPD. METHODS: Six exacerbated COPD patients that were randomised to receiving HaH care and three patients randomised to receiving traditional hospital care were interviewed in semi-structured in-depth interviews. Four spouses were present during the respective patients' interviews. The interviews were audio-taped, transcribed and analysed by a four-step method for systematic text condensing. RESULTS: Despite limited assistance from the health care service, the patients and their spouses experienced the HaH treatment as safe. They expressed that information that was adapted to specific situations in their daily lives and given in a familiar environment had positive impact on their self-management of COPD. CONCLUSION: The results contribute to increased knowledge and awareness about what the patients experienced as important aspects of a HaH treatment programme. How adapted input from health services can make patients with exacerbation of COPD feel safe and better able to manage their disease, is important knowledge for developing new and effective health services for patients with chronic disease.     

慢性阻塞性肺疾病患者继发肺部真菌感染的临床分析

目的探讨慢性阻塞性肺疾病(COPD)患者继发肺部真菌感染的临床特点。方法回顾性分析2008年1月到2010年12月安徽医科大学第一附属医院收治的COPD继发肺部真菌感染患者病例,并对其耐药情况进行比较。结果本组199例COPD患者检出白色念珠菌137例(68.84%),光滑念珠菌32例(16.08%),热带念珠菌17例(8.54%),克柔念珠菌9例(4.52%),毛霉菌3例(1.51%),清酒假丝酵母菌1例(0.50%);白色念珠菌检出率有下降趋势,热带念珠菌有上升趋势;196例真菌对伏立康唑、氟康唑、两性霉素B、伊曲康唑、氟胞嘧啶的耐药率分别为3.6%、5.1%、1.0%、8.7%和0;2008年至2010年白色念珠菌和光滑念珠菌耐药率变化差异无统计学意义。结论 COPD患者继发肺部真菌感染病原菌仍以白色念珠菌为主,其次为光滑念珠菌和热带念珠菌;白色念珠菌和光滑念珠菌耐药率无明显改变。     

Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study

Background

The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO₂) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO₂ and mortality in oxygen-dependent COPD.

Methods

National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO₂ while breathing air, PaCO₂ (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO₂), World Health Organization performance status, body mass index, comorbidity, and medications.

Results

Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO₂ (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO₂ (air) 6.5 kPa and increased mortality at PaCO₂ (air) below 5.0 kPa and above 7.0 kPa.

Conclusion

In oxygen-dependent COPD, PaCO₂ (air) is an independent prognostic factor with a U-shaped association with mortality.     

Risk of herpes zoster among patients with chronic obstructive pulmonary disease: a population-based study

Background

Systemic inflammation and dysregulated immune function in chronic obstructive pulmonary disease (COPD) is hypothesized to predispose patients to development of herpes zoster. However, the risk of herpes zoster among patients with COPD is undocumented. We therefore aimed to investigate the risk of herpes zoster among patients with COPD.

Methods

We conducted a cohort study using data from the Taiwan Longitudinal Health Insurance Database. We performed Cox regressions to compare the hazard ratio (HR) of herpes zoster in the COPD cohort and in an age- and sex-matched comparison cohort. We divided the patients with COPD into three groups according to use of steroid medications and performed a further analysis to examine the risk of herpes zoster.

Results

The study included 8486 patients with COPD and 33 944 matched control patients. After adjustment for potential confounding factors, patients with COPD were more likely to have incidents of herpes zoster (adjusted HR 1.68, 95% confidence interval [CI] 1.45–1.95). When compared with the comparison cohort, the adjusted HR of herpes zoster was 1.67 (95% CI 1.43–1.96) for patients with COPD not taking steroid medications. The adjusted HR of herpes zoster was slightly greater for patients with COPD using inhaled corticosteroids only (adjusted HR 2.09, 95% CI 1.38–3.16) and was greatest for patients with COPD using oral steroids (adjusted HR 3.00, 95% CI 2.40–3.75).

Interpretation

Patients with COPD were at increased risk of herpes zoster relative to the general population. The relative risk of herpes zoster was greatest for patients with COPD using oral steroids.Herpes zoster is caused by a reactivation of latent varicella-zoster virus residing in sensory ganglia after an earlier episode of varicella.¹ Herpes zoster is characterized by a painful vesicular dermatomal rash. It is commonly complicated with chronic pain (postherpetic neuralgia), resulting in reduced quality of life and functional disability to a degree comparable to that experienced by patients with congestive heart failure, diabetes mellitus and major depression.^1,2 Patients with herpes zoster experience more substantial role limitations resulting from emotional and physical problems than do patients with congestive heart failure or diabetes.³ Pain scores for postherpetic neuralgia have been shown to be as high as those for chronic pain from osteoarthritis and rheumatoid arthritis.³ Although aging is the most well-known risk factor for herpes zoster, people with diseases associated with impaired immunity, such as malignancy, HIV infection, diabetes and rheumatic diseases, are also at higher risk for herpes zoster.^4,5Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation that is associated with an abnormal inflammatory response by the small airways and alveoli to inhaled particles and pollutants.⁶ Disruption of local defence systems (e.g., damage to the innate immune system, impaired mucociliary clearance) predispose patients with COPD to respiratory tract infections. Each infection can cause exacerbation of COPD and further deterioration of lung function, which in turn increase predisposition to infection.^7,8There is increasing evidence that COPD is an autoimmune disease, with chronic systemic inflammation involving more than just the airways and lungs.⁶ Given that various immune-mediated diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) have been reported to be associated with an increased risk of herpes zoster,^4,9,10 it is reasonable to hypothesize that the immune dysregulation found in COPD may put patients at higher risk of developing herpes zoster. In addition, inhaled or systemic corticosteroids used for management of COPD can increase susceptibility to herpes zoster by suppressing normal immune function.¹¹ However, data are limited regarding the risk of herpes zoster among patients with COPD.The goal of our study was to investigate whether patients with COPD have a higher incidence of herpes zoster than the general population. In addition, we aimed to examine the risk for herpes zoster with and without steroid therapy among patients with COPD relative to the general population.     

Metallic elements in exhaled breath condensate and serum of patients with exacerbation of chronic obstructive pulmonary disease

Biomarkers in exacerbated chronic obstructive pulmonary disease may be useful in aiding diagnosis, defining specific phenotypes of disease, monitoring the disease and evaluating the effects of drugs. The aim of this study was the characterization of metallic elements in exhaled breath condensate and serum as novel biomarkers of exposure and susceptibility in exacerbated chronic obstructive pulmonary disease using reference analytical techniques. C-Reactive protein and procalcitonin were assessed as previously validated diagnostic and prognostic biomarkers which have been associated with disease exacerbation, thus useful as a basis of comparison with metal levels. Exhaled breath condensate and serum were obtained in 28 patients at the beginning of an episode of disease exacerbation and when they recovered. Trace elements and toxic metals were measured by inductively coupled plasma-mass spectrometry. Serum biomarkers were measured by immunoassay. Exhaled manganese and magnesium levels were influenced by exacerbation of chronic obstructive pulmonary disease, an increase in their concentrations--respectively by 20 and 50%--being observed at exacerbation in comparison with values obtained at recovery; serum elemental composition was not modified by exacerbation; serum levels of C-reactive protein and procalcitonin at exacerbation were higher than values at recovery. In outpatients who experienced a mild-moderate chronic obstructive pulmonary disease exacerbation, manganese and magnesium levels in exhaled breath condensate are elevated at admission in comparison with values at recovery, whereas no other changes were observed in metallic elements at both the pulmonary and systemic level.     

Low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong: A cohort study

BackgroundEvidence suggests that chronic obstructive pulmonary disease (COPD) is associated with a higher risk of lung carcinoma. Using a territory-wide clinical electronic medical records system, we investigated the association between low-dose aspirin use (≤160 mg) among patients with COPD and incidence of lung carcinoma and the corresponding risk of bleeding.Methods and findingsThis is a retrospective cohort study conducted utilizing Clinical Data Analysis Reporting System (CDARS), a territory-wide database developed by the Hong Kong Hospital Authority. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between aspirin nonusers (35,049 patients) with new aspirin users (7,679 patients) among all eligible COPD patients from 2005 to 2018 attending any public hospitals. The median age of the cohort was 75.7 years (SD = 11.5), and 80.3% were male. Competing risk regression with Cox proportional hazards model were performed to estimate the subdistribution hazard ratio (SHR) of lung carcinoma with low-dose aspirin and the associated bleeding events. Of all eligible patients, 1,779 (4.2%, 1,526 and 253 among nonusers and users) were diagnosed with lung carcinoma over a median follow-up period of 2.6 years (interquartile range [IQR]: 1.4 to 4.8). Aspirin use was associated with a 25% lower risk of lung carcinoma (SHR = 0.75, 95% confidence interval [CI] 0.65 to 0.87, p = <0.001) and 26% decrease in lung carcinoma–related mortality (SHR = 0.74, 95% CI 0.64 to 0.86, p = <0.001). Subgroup analysis revealed that aspirin was beneficial for patients aged above or below 75 years, but was also beneficial among populations who were male, nondiabetic, and nonhypertensive. Aspirin use was not associated with an increased risk of upper gastrointestinal bleeding (UGIB) (SHR = 1.19, 95% CI 0.94 to 1.53, p = 0.16), but was associated with an increased risk of hemoptysis (SHR = 1.96, 95% CI 1.73 to 2.23, p < 0.001). The main limitations of the study were (i) that one group of patients may be more likely to seek additional medical attention, although this was partially mitigated by the use of propensity score analysis; and (ii) the observational nature of the study renders it unable to establish causality between aspirin use and lung carcinoma incidence.ConclusionsIn this study, we observed that low-dose aspirin use was associated with a lower risk of lung carcinoma and lung carcinoma–related mortality among COPD patients. While aspirin was not associated with an increased risk of UGIB, the risk of hemoptysis was elevated.

In a cohort study, Si-Yeung Yu and colleagues investigate the association between low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong.     

Systemic inflammation in chronic obstructive pulmonary disease: a population-based study

Background

Investigations on pulmonary macrophages (MΦ) mostly focus on alveolar MΦ (AM) as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue.

Methods

Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay.

Results

IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6.

Conclusion

AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response.     

Gait mechanics in patients with chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is characterized by the frequent association of disease outside the lung. The objective of this study was to determine the presence of biomechanical gait abnormalities in COPD patients compared to healthy controls while well rested and without rest.

Methods

Patients with COPD (N = 17) and aged-matched, healthy controls (N = 21) walked at their self-selected pace down a 10-meter walkway while biomechanical gait variables were collected. A one-minute rest was given between each of the five collected trials to prevent tiredness (REST condition). Patients with COPD then walked at a self-selected pace on a treadmill until the onset of self-reported breathlessness or leg tiredness. Subjects immediately underwent gait analysis with no rest between each of the five collected trials (NO REST condition). Statistical models with and without covariates age, gender, and smoking history were used.

Results

After adjusting for covariates, COPD patients demonstrated more ankle power absorption in mid-stance (P = 0.006) than controls during both conditions. Both groups during NO REST demonstrated increased gait speed (P = 0.04), stride length (P = 0.03), and peak hip flexion (P = 0.04) with decreased plantarflexion moment (P = 0.04) and increased knee power absorption (P = 0.04) as compared to REST. A significant interaction revealed that peak ankle dorsiflexion moment was maintained from REST to NO REST for COPD but increased for controls (P < 0.01). Stratifying by disease severity did not alter these findings, except that step width decreased in NO REST as compared to REST (P = 0.01). Standardized effect sizes of significant effects varied from 0.5 to 0.98.

Conclusions

Patients with COPD appear to demonstrate biomechanical gait changes at the ankle as compared to healthy controls. This was seen not only in increased peak ankle power absorption during no rest but was also demonstrated by a lack of increase in peak ankle dorsiflexion moment from the REST to the NO REST condition as compared to the healthy controls. Furthermore, a wider step width has been associated with fall risk and this could account for the increased incidence of falls in patients with COPD.     

慢性阻塞性肺疾病急性加重患者下呼吸道病原菌分析

目的了解慢性阻塞性肺疾病急性加重患者（AECOPD）下呼吸道感染病原菌的特点及耐药情况,为临床合理选择抗菌药物提供借鉴。方法取诸暨市人民医院2005年1月至2009年12月住院的273例AECOPD患者的下呼吸道痰标本及纤支镜刷取分泌物进行培养、鉴定、药敏,并对结果进行分析。结果273例AECOPD患者中有225例患者分离到病原菌,分离病原菌282株。病原菌中革兰阴性杆菌最多,占46．8％,依次为铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌等;革兰阳性球菌占18．4％,以金黄色葡萄球菌最多,肠球菌、肺炎链球菌次之;真菌占20．9％;流感嗜血杆菌占13．8％。药敏结果显示阴性杆菌对美罗培意敏感率最好,其次为亚胺培南、哌拉西林．他唑巴坦。结论AECOPD患者下呼吸道病原菌以革兰阴性杆菌为主,耐药现象明显,流感嗜血杆菌已经成为AECOPD患者重要的致病菌之一。     

功率自行车下肢亚极量运动对慢性阻塞性肺疾病康复影响的临床报告*

目的: 研究慢性阻塞性肺疾病（COPD）患者功率自行车下肢亚极量运动的康复治疗效果。方法: 30例门诊COPD患者随机分为康复组和对照组,每组15例,康复前后均完成常规肺功能（PFT）、心肺运动试验（CPET）、血气分析（ABG）、呼吸困难Borg评分和COPD患者自我评估测试问卷（CAT评分）,并比较前后变化。康复组采用功率自行车锻炼,以CPET80%峰值功率强度,每次运动30 min,每周3次,完成12周。结果: 康复组在康复后IC显著提高(P<0.01),peakW和peakVO₂也显著提高(P<0.01);Borg评分和CAT评分显著降低 (P<0.01)。末次运动持续时间较首次明显延长(P<0.01)。而对照组的这些指标均无显著改变(P>0.05)。两组在康复前后的PFT指标和血气分析等参数无明显变化。结论: COPD患者可以安全有效地进行运动康复治疗。功率自行车下肢亚极量运动康复能使COPD患者整体功能改善、运动时间延长、生活质量提高、患者获益。     

慢性阻塞性肺疾病急性加重期病原学及细菌药性分析

目的:探讨慢性阻塞性肺疾病急性加重期病原学特点及细菌耐药情况,为临床合理使用抗生素提供科学依据。方法:回顾性分析我院呼吸内科和老年学科2008年1月-2009年1月563例慢性阻塞性肺疾病(急性加重期)住院患者痰培养及药敏试验结果。结果:563例患者中检出阳性结果205例,检出率为36.41%。其中G+菌46例、G-菌119例、真菌40例。G+菌以金黄色葡萄球菌最多(14例),其次为表皮葡萄球菌和草绿色链球菌;G-菌以铜绿假单胞菌最多(37例),其次为克雷伯菌;真菌以白色念珠菌最多(20例)。G-杆菌对氨苄西林、哌拉西林、头孢唑啉、复方新诺明耐药严重,对亚胺培南、含β-内酰胺酶抑制剂的联合制剂较敏感。金黄色葡萄球菌对多种抗生素严重耐药,对万古霉素、亚胺培南较敏感。真菌对氟康唑敏感占50.81%,对伊曲康唑敏感占30.12%,对酮康唑敏感占30.83%,对5-氟胞嘧啶敏感占10.74%。结论:慢性阻塞性肺疾病急性加重期以G-为主,真菌感染有增多趋势,病原菌呈现多重耐药现象。     

Alterations of plasma inflammatory biomarkers in the healthy and chronic obstructive pulmonary disease patients with or without acute exacerbation

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortally and morbidity, associated with acute exacerbations (AECOPD) resulted from smoking, infection or air pollution. Systemic inflammation has been considered as one of major pathophysiologic alterations in AECOPD. The present study aimed at developing disease-specific biomarker evaluation by integrating proteomic profiles of inflammatory mediators in AECOPD with clinical and biological informatics. Plasma samples from 18 subjects including healthy people or patients with stable COPD or AECOPD were collected to measure 507 inflammatory mediators using antibody microarray. Clinical informatics was achieved by a Digital Evaluation Score System (DESS) for assessing severity of patients. 20 mediators were significantly different between 3 groups (p<0.05), of which, Cerberus 1, Growth Hormone R, IL-1F6, IL-17B R, IL-17D, IL-19, Lymphotoxin beta, MMP-10, Thrombopoietin and TLR4 were correlated with DESS scores (p<0.05). There was a down-regulation of systemic inflammatory responses in AECOPD. The integration of proteomic profile with clinical informatics as part of clinical bioinformatics is important to screen disease-specific and disease-staged biomarkers. This article is part of a Special Issue entitled: Proteomics: The clinical link.     

Incidence and risk factors of serious adverse events during antituberculous treatment in Rwanda: a prospective cohort study

Background

Tuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa.In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome.

Methods and findings

Prospective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009.Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28–40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm³ (IQR 44–248 cells/mm³). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23).HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4–8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1–3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1–3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0–2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3–3.0).

Conclusion

Adverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections.     

Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis

Background

Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease. Recent studies suggested an association between COPD and polymorphisms in CHRNA coding subunits of nicotinic acetylcholine receptor. Herein, we performed a meta-analysis to clarify the impact of CHRNA variants on COPD.

Methods

We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on CHRNA. Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group.

Results

Among seven reported variants in CHRNA, rs1051730 was finally analyzed with sufficient studies. Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed. A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10^-5). At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10^-5). Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001).

Conclusions

Our findings suggest that rs1051730 in CHRNA is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction.