Pulmonary scar carcinoma in South Africa

Background. The association between lung scarring and the subsequent development of cancer remains controversial. South Africa has one of the highest incidences of tuberculosis in the world, and resultant scarring may predispose to malignancy. The country also carries a very high burden of smoking and smoking-related diseases that may be synergistic in malignant transformation.Objective. To assess the frequency of pulmonary scarring in patients with lung cancer.Methods. All patients with confirmed lung cancer and a staging computed tomography (CT) scan of the chest were included in this 2-year retrospective study. Pulmonary scarring was categorised according to location as present in: (i) the same lobe as the primary tumour, (ii) a different lobe of the same lung, or (iii) the contralateral lung; or (iv) as diffuse. Post-obstructive bronchiectasis and other changes secondary to cancer were considered not to represent scarring.Results. We identified 435 cases of primary lung cancer. In total, 95 patients (21.8%) had CT evidence of pulmonary scarring. Eighty-three of 85 patients (97.6%) had focal scarring in the same lobe as the primary tumour. Of these, 37 (43.5%) also had scarring involving a different lobe of the same lung, whereas only one (1.2%; p<0.001) had scarring isolated to a different lobe of the same lung. Moreover, 21 patients (24.7%) also had scarring of the opposite lung, but only one patient (1.2%; p<0.001) had scarring isolated to the contralateral lung. Ten patients had diffuse scarring, caused by bronchiectasis (n=5), idiopathic pulmonary fibrosis (n=4) and silicosis (n=1).Conclusion. At least one in five patients with lung cancer had scarring, which was significantly more likely to be present in the same lobe as the tumour, suggesting a predisposition to malignancy

A severity-of-illness score in patients with tuberculosis requiring intensive care

Background. We previously retrospectively validated a 6-point severity-of-illness score aimed at identifying patients at risk of dying of tuberculosis (TB) in the intensive care unit (ICU). Parameters included septic shock, HIV infection with a CD4 count <200 cells/µL, renal dysfunction, a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (P/F) <200 mmHg, a chest radiograph demonstrating diffuse parenchymal infiltrates, and no TB treatment on admission.Objectives. To prospectively validate the severity-of-illness scoring system in patients with TB requiring intensive care, and to refine and simplify the score in order to expand its clinical utility.Methods. We performed a prospective observational study with a planned post hoc retrospective analysis, enrolling all adult patients with confirmed TB admitted to the medical ICU of a tertiary hospital in Cape Town, South Africa, from 1 February 2015 to 31 July 2018. The admission data of all adult patients with TB requiring admission to the ICU were used to calculate the 6-point severity-of-illness score and a refined 4-point score (based on the planned post hoc analysis). Descriptive statistics and χ2 or Fisher’s exact tests (where indicated) were performed on dichotomous categorical variables, and t-tests on continuous data. Patients were categorised as hospital survivors or non-survivors.Results. Forty-one of 78 patients (52.6%) died. The 6-point scores of non-survivors were higher than those of survivors (mean (standard deviation (SD)) 3.5 (1.3) v. 2.7 (1.2); p=0.01). A score ≥3 v. <3 was associated with increased mortality (64.0% v. 32.1%; odds ratio (OR) 3.75; 95% confidence interval (CI) 1.25 - 10.01; p=0.01). Post hoc, a P/F ratio <200 mmHg and no TB treatment on admission failed to predict mortality, whereas any immunosuppression did. A revised 4-point score (septic shock, any immunosuppression, acute kidney injury and lack of lobar consolidation) demonstrated higher scores in non-survivors than survivors (mean (SD) 2.8 (1.1) v. 1.6 (1.1); p<0.001). A score ≥3 v. ≤2 was associated with increased mortality (78.4% v. 29.3%; OR 8.76; 95% CI 3.12 - 24.59; p<0.001).Conclusions. The 6-point severity-of-illness score identified patients at increased risk of death. We were able to derive and retrospectively validate a simplified 4-point score with superior predictive power

Predictors of treatment success in smoking cessation with varenicline combined with nicotine replacement therapy v. varenicline alone

Background. Identification of the predictors of treatment success in smoking cessation may help healthcare workers to improve the effectiveness of attempts at quitting.Objective. To identify the predictors of success in a randomised controlled trial comparing varenicline alone or in combination with nicotine replacement therapy (NRT).Methods. A post-hoc analysis of the data of 435 subjects who participated in a 24-week, multicentre trial in South Africa was performed. Logistic regression was used to analyse the effect of age, sex, age at smoking initiation, daily cigarette consumption, nicotine dependence, and reinforcement assessment on abstinence rates at 12 and 24 weeks. Point prevalence and continuous abstinence rates were self-reported and confirmed biochemically with exhaled carbon monoxide readings.Results. The significant predictors of continuous abstinence at 12 and 24 weeks on multivariate analysis were lower daily cigarette consumption (odds ratio (OR) 1.86, 95% confidence interval (CI) 1.21 - 2.87, p=0.005 and OR 1.83, 95% CI 1.12 - 2.98, p=0.02, respectively) and older age (OR 1.52, 95% CI 1.00 - 2.31, p=0.049 and OR 1.79, 95% CI 1.13 - 2.84, p=0.01, respectively). There was no difference in the predictors of success in the univariate analysis, except that older age predicted point prevalence abstinence at 12 weeks (OR 1.47, 95% CI 1.00 - 2.15, p=0.049). The findings were inconclusive for an association between abstinence and lower nicotine dependence, older age at smoking initiation and positive reinforcement.Conclusion. Older age and lower daily cigarette consumption are associated with a higher likelihood of abstinence in patients using varenicline, regardless of the addition of NRT

The impact of an electronic clinical decision support for pulmonary embolism imaging on the efficiency of computed tomography pulmonary angiography utilisation in a resource-limited setting

Background. Pulmonary embolism (PE) is associated with high morbidity and mortality. Effective intervention requires prompt diagnosis. Computed tomography pulmonary angiography (CTPA) is sensitive and specific for PE and is the investigation of choice. Inappropriate CTPA utilisation results in unnecessary high radiation exposure and is costly. State­of­the­art electronic radiology workflow can provide clinical decision support (CDS) for specialised imaging requests, but there has been limited work on the clinical impact of CDS in PE, particularly in resource­constrained environments. Objective. To determine the impact of an electronic CDS for PE on the efficiency of CTPA utilisation in a resource­limited setting. Methods. In preparation, a PE diagnostic algorithm was distributed to hospital clinicians, explaining the combined role of the validated modified Wells score and the quantitative D­dimer test in defining the pre­test probability of PE. Thereafter, an automated, electronic CDS was introduced for all CTPA requests. Total CTPA referrals and the proportion positive for PE were assessed for three study phases: (i) pre­ diagnostic algorithm; (ii) post­algorithm, pre­CDS; and (iii) post­CDS.Results. The proportion of CTPAs positive for PE after CDS implementation was almost double that prior to introduction of the diagnostic algorithm (phase 1 v. 3, 17.4% v. 30.7%; p=0.036), with a correspondingly significant decrease in the proportion of non­positive CTPAs (phases 1 v. 3, 82.6% v. 69.3%; p=0.015) During phases 2 and 3, no CTPAs were requested for patients with a modified Wells score of ≤4 and a documented negative D­dimer, indicating adherence to the algorithm.Conclusion. Implementing an electronic CDS for PE significantly increased the efficiency of CTPA utilisation and significantly decreased the proportion of inappropriate scans.

The impact of HIV infection on the presentation of lung cancer in South Africa

Background. Despite the very high background prevalence of HIV and smoking-related diseases in sub-Saharan Africa, very little is known about the presentation of lung cancer in HIV-infected individuals.Methods. We prospectively compared HIV-positive (n=44) and HIV-negative lung cancer patients (n=425) with regard to demographics, cell type, performance status and umour node metastasis staging at initial presentation.Results. HIV-positive patients were found to be younger than HIV-negative (mean 54.1 (standard deviation (SD) 8.4) years v. 60.5 (10) years, p<0.01), more likely to have squamous cell carcinoma (43.2% v. 30.1%, p=0.07) and significantly more likely to have a poor Eastern Cooperative Oncology Group (ECOG) performance status of ≥3 (47.7% v. 29.4%, p=0.02). In the case of non-small cell-lung cancer, they were also significantly less likely to have early stage lung cancer (0% v. 10.3%, p=0.02) compared with HIV-negative patients.Conclusions. HIV-positive lung cancer patients were younger, significantly more likely to have a poor performance status at presentation and significantly less likely to have early stage lung cancer when compared with HIV-negative patients

Smoking in asthma is associated with elevated levels of corticosteroid resistant sputum cytokines—an exploratory study

<p>Background: Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.</p> <p>Objectives: To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.</p> <p>Methods: Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.</p> <p>Results: Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers wi</p> <p>Conclusion: Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.</p&gt

The current aetiology of malignant pleural effusion in the Western Cape Province, South Africa

Background. Malignant pleural effusion (MPE) represents a very common cause of pleural exudates, and is one of the most challenging pleural disorders to manage. This could be attributed to the paucity of high-quality experimental evidence, and inconsistent practice worldwide. South Africa (SA) currently has no data regarding the aetiology of MPE.Objectives. To identify the most common malignancies causing MPE in a population served by a large tertiary hospital in SA, and specifically the relative contribution of mesothelioma. A secondary objective was to evaluate the efficacy of chemical pleurodesis in a subset of patients.Methods. We retrospectively included all known cases of MPE evaluated at our institution over a 3-year period with a tissue diagnosis of MPE.Results. The most common causes of MPE in a total of 274 patients were lung cancer (n=174, 63.5%), breast cancer (n=32, 11.7%), unknown primary (n=22, 11.7%) and mesothelioma (n=27, 9.9%). Talc pleurodesis was performed in 81 of 194 patients (41.8%) referred to our division, and was radiologically successful in 22 of 25 (88.0%) followed up to 3 months.Conclusions. The main cause of MPE in our setting was lung cancer, followed by breast cancer, unknown primary and mesothelioma. Chemical pleurodesis was a viable palliative measure for MPE in this population

Guideline for the management of acute asthma in adults: 2013 update

Acute asthma attacks (asthma exacerbations) are increasing episodes of shortness of breath, cough, wheezing or chest tightness associated with a decrease in airflow that can be quantified and monitored by measurement of lung function (peak expiratory flow (PEF) or forced expiratory volume in the 1st second) and requiring emergency room treatment or admission to hospital for acute asthma and/or systemic glucocorticosteroids for management. The goals of treatment are to relieve hypoxaemia and airflow obstruction as quickly as possible, restore lung function, and provide a suitable plan to avoid relapse. Severe exacerbations are potentially life-threatening and their treatment requires baseline assessment of severity, close monitoring, and frequent reassessment using objective measures of lung function (PEF) and oxygen saturation. Patients at high risk of asthma-related death require particular attention. First-line therapy consists of oxygen supplementation, repeated administration of inhaled short-acting bronchodilators (beta-2-agonists and ipratropium bromide), and early systemic glucocorticosteroids. Intravenous magnesium sulphate and aminophylline are second- and third-line treatment strategies, respectively, for poorly responding patients. Intensive care is indicated for severe asthma that is not responsive to first-line treatment. Antibiotics are only indicated when there are definite features of bacterial infection. Factors that precipitated the acute asthma episode should be identified and preventive measures implemented. Acute asthma is preventable with optimal control of chronic asthma