Lung volume reduction in chronic obstructive pulmonary disease

Pathognomonic features of advanced emphysema include a markedly reduced alveolar surface area due to the formation of blebs and bullae and significantly reduced elastic recoil. The aim of lung volume  reduction, which can be achieved by either surgery or endoscopic techniques, is volume loss of the targeted, diseased region(s) and redirecting airflow to less affected regions. Lung volume reduction surgery (LVRS) entails reducing the lung volume by wedge excision of  emphysematous tissue. LVRS  carries significant morbidity and mortality, but can offer survival benefit and increased exercise capacity in selected patients with predominantly upper-lobe emphysema and low exercise capacity. Endoscopic lung volume reduction (ELVR) refers to bronchoscopically inducing volume loss to  improve pulmonary mechanics and compliance, thereby reducing the work of breathing. Globally, this technique is increasingly used as treatment for advanced  emphysema with the objective of obtaining similar functional advantages to surgical lung volume reduction, while decreasing risks and costs. Current evidence  suggests that patients with either homogeneous or  heterogeneous disease may benefit from ELVR. It remains paramount that a systematic approach is followed and selection criteria are met, given the high costs and potential complications related to both LVRS and ELVR

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

Tricyclic antidepressant overdose necessitating ICU admission

Tricyclic antidepressant (TCA) overdose necessitating intensive care unit (ICU) admission remains a significant problem in the Western Cape. In this retrospective study, we reviewed the course of life-threatening TCA overdose in our centre to identify potential prognostic indicators. TCA levels >1 000 ng/ml were associated with QT and QRS prolongation and convulsions. However, no single parameter predicted non-survival. The overall mortalityof TCA overdose was very low. Our findings should encourage clinicians to offer medical care including ICU admission, if necessary, to patients with TCA overdose

Case Report: The real value of endobronchial ultrasound

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become a standard procedure worldwide, used in conjunction with bronchoscopy to obtain biopsies for mediastinal disorders. A 67-year-old man with a 40 pack-year smoking history presented with a 2-year history of hoarseness and weight loss. He also had a history of asbestos exposure. On examination under anaesthesia a lesion of the right false vocal fold was found and histology showed a moderately differentiated infiltrating keratinising squamous carcinoma. The question posed was whether this mass could be ascribed to metastatic supraglottic carcinoma or if it was indeed a metachronous primary bronchus carcinoma, as the treatment of these two malignancies differs significantly. Traditional bronchoscopy with TBNA is the least invasive procedure to obtain a cytological diagnosis, but the proximity of the aorta and pulmonary arteries and the mass being 14 mm from the bronchus would have made sampling by means of this procedure near impossible. We used EBUS to localise the mass and noted the position of the major vessels on Doppler ultrasound. Real-time ultrasound guidance allowed us to bridge the tissue plane between the mass and bronchial lumen using the longer EBUS needle and to obtain a fine-needle aspirate of the mass, which proved to be a keratinising squamous carcinoma. We describe this case in which EBUS-TBNA was pivotal in reducing the number of invasive procedures in a patient with metastatic supraglottic carcinoma

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 smokinginitiation 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

Lack of association of glycated haemoglobin with blood pressure and subclinical atherosclerosis in black South Africans: a five-year prospective study

Objectives: Hypertension and diabetes are common in rapidly urbanising sub-Saharan African communities. However, lack of longitudinal data in these regions prevents adequate analysis of the link between measures of glycaemia and cardiovascular disease. Therefore, we examined the relationships of fasting glucose and glycated haemoglobin (HbA1c) with brachial and central blood pressure (BP), and measures of vascular structure and function after five years in black South Africans.Setting and subjects: Nine hundred and twenty-eight participants were included as part of the Prospective Urban Rural Epidemiological (PURE) study in the North West Province.Outcome measures: Fasting glucose, HbA1c and brachial BP at two time points were determined. Central BP, augmentation index (AI) and carotid intima-media thickness (CIMT) were taken at follow-up.Results: Fasting glucose [4.78 (3.50, 6.30) vs. 5 mmol/l (3.96, 6.42)]; HbA1c [5.6 (4.9, 6.3) vs. 5.9% (5.2, 6.9) and (37 vs. 41 mmol/mol)]; and BP (134/88.1 vs. 138/89.5 mmHg) increased significantly over five years (p-value < 0.05). However, an association was absent between BP, AI or CIMT and either baseline or the five-year change in glucose or HbA,sub>1c. Multivariate analyses confirmed that neither glucose or HbA1c predicted changes in BP, CIMT or AI, but factors that did associate significantly were age, male gender, rural location, abdominal obesity, alcohol intake, total cholesterol to high-density lipoprotein ratio, C-reactive protein and antihypertensive medication (R2, ranging from 0.24-0.36).Conclusion: Although both BP and measures of glycaemia increased significantly over five years in black South Africans, glucose was not independently associated with BP or measures of large artery structure or function. We suggest that fasting glucose and HbA1c below the threshold of diagnosing diabetes should not be used in isolation to predict cardiovascular risk in African individuals.Keywords: fasting glucose, glycated haemoglobin, ethnicity, atherosclerosis, longitudina

Experimental evidence for sulphide magma percolation and evolution : relevant to the chromite bearing reefs of the Bushveld Complex

Thesis (MSc)--Stellenbosch University, 2012.ENGLISH ABSTRACT: Pt mineralization within the Bushveld Complex is strikingly focused on the chromitite reefs, despite these horizons being associated with low volumes of base metal sulphide relative to Pt grade. Partitioning of Pt (Dsil/sulp) from silicate magma into immiscible sulphide liquid appears unable to explain Pt concentrations in chromitite horizons, due to the mismatch that exists between very large R factor required and the relevant silicate rock volume. Consequently, in this experimental study we attempt to gain better insight into possible Pt grade enhancement processes that may occur with the Bushveld Complex (BC) sulphide magma. We investigate the wetting properties of sulphide melt relevant to chromite and silicate minerals, as this is a key parameter controlling sulphide liquid percolation through the cumulate pile. Additionally, we have investigated how fractionation of the sulphide liquid from mono-sulphide-solid-solution (Mss) crystals formed within the overlying melanorite might affect sulphide composition and Pt grades within the evolved sulphide melt. Two sets of experiments were conducted: Firstly, at 1 atm to investigate the phase relations between 900OC and 1150OC, within Pt-bearing sulphide magma relevant to the BC; Secondly, at 4 kbar, between 900OC to 1050OC, which investigated the downwards percolation of sulphide magma through several layers of silicate (melanorite) and chromitite. In addition, 1atm experiments were conducted within a chromite dominated chromite-sulphide mixture to test if interaction with chromite affects the sulphide system by ether adding or removing Fe2+. Primary observations are as follows: We found sulphide liquid to be extremely mobile, the median dihedral angles between sulphide melt and the minerals of chromitite and silicate layers are 11O and 33O respectively. This is far below the percolation threshold of 60O for natural geological systems. In silicate layers sulphide liquid forms vertical melt networks promoting percolation. In contrast, the extremely effective wetting of sulphide liquid in chromitites restricts sulphide percolation. Inter-granular capillary forces increase melt retention, thus chromitites serve as a reservoir for sulphide melt. Sulphide liquid preferentially leaches Fe2+ from chromite, increasing the Fe concentration of the sulphide liquid. The reacted chromite rims are enriched in spinel end-member. This addition of Fe2+ to the sulphide magma prompts crystallization Fe-rich Mss, decreasing the S-content of sulphide melt. This lowers Pt solubility and leads to the formation of Pt alloys within the chromitite layer. Eventually, Cu-rich sulphide melt escapes through the bottom of the chromitite layer. These observations appear directly applicable to the mineralized chromitite reefs of the Bushveld complex. We propose that sulphide magma, potentially injected from the mantle with new silicate magma injections, percolated through the silicate cumulate overlying the chromitite and crystallized a significant volume of Fe-Mss. Chromitite layers functioned as traps for percolating, evolved, Cu-, Ni- and Pt-rich sulphide liquids. This is supported by the common phenomenon that chromitites contain higher percentages of Ni, Cu and Pt relative to hanging wall silicate layers. When in contact with chromite, sulphide melt is forced to crystallize Mss as it leaches Fe2+ from the chromite, thereby further lowering the S-content of the melt. This results in precipitation, as Pt alloys, of a large proportion of the Pt dissolved in the sulphide melt. In combination, these processes explain why chromitite reefs in the Bushveld Complex have Pt/S ratios are up to an order of magnitude higher that adjacent melanorite layers.AFRIKAANSE OPSOMMING: Pt mineralisasie in die Bosveld Kompleks is kenmerkend gefokus op die chromatiet riwwe, alhoewel die riwwe geassosieer is met lae volumes basismetaal sulfiedes relatief tot Pt graad. Verdeling van Pt (Dsil/sulp) vanaf silikaat magma in onmengbare sulfiedvloeistof is klaarblyklik onvoldoende om Pt konsentrasies in chromatiet lae te verduidelik, a.g.v. die wanverhouding wat bestaan tussen ‘n baie groot R-faktor wat benodig word en die relatiewe silikaat rots volumes. Gevolglik, in die eksperimentele studie probeer ons beter insig kry oor moontlike Pt graad verhogingsprosesse wat plaasvind in die BK sulfied magma. Ons ondersoek die benattingseienskappe van sulfied vloeistof relevant tot chromiet- en silikaat minerale, omdat dit die sleutel maatstaf is vir die beheer van sulfied vloeistof deursypeling deur die kumulaat opeenhoping. Addisioneel het ons ook ondersoek hoe die fraksionering van sulfied vloeistof vanaf MSS kristalle, gevorm binne die hangende melanoriet muur, moontlik die sulfied samestelling en Pt graad binne ontwikkelde sulfied smelt kan beïnvloed. Twee stelle van eksperimente is gedoen: Eerstens, by 1 atm om ondersoek in te stel oor fase verwantskappe tussen 900OC en 1150OC, binne ‘n Pt-verrykte sulfied magma samestelling relevant tot die BK; Tweedens, by 4 kbar, tussen 900OC tot 1050OC, wat die afwaartse deursypeling van sulfied magma deur veelvuldige lae van silikaat minerale en chromatiet. Addisionele 1 atm eksperimente is gedoen binne ‘n chromiet gedomineerde chromiet-sulfied mengsel, om te toets of interaksie met chromiet die sulfied sisteem affekteer deur Fe2+ te verwyder of by te dra. Primêre observasies is soos volg: Ons het bevind sulfiedsmelt is uiters mobiel, die mediaan dihedrale hoek tussen sulfiedsmelt en minerale van chromiet en silikaat lae is 11O en 33O onderskydelik. Dit is ver onder die deursypelings drumpel van 60O vir natuurlike geologiese stelsels. In silikaatlae vorm die sulfiedsmelt vertikale netwerke wat deursypeling bevorder. Inteendeel, uiters effektiewe benatting van sulfiedsmelt binne chromatiete vertraag sulfied deusypeling. Tussen kristal kapilêre kragte verhoog smelt retensie, dus dien chromatiete as ‘n opgaarmedium vir sulfiedsmelt. S oorversadigte sulfied vloeistof loogsif Fe2+ vanuit chromiet en veroorsaak ‘n verhoging in Fe-konsentraie. Die gereageerde chromiet buiterante is daarvolgens verryk in Cr-spinêl eind-ledemaat. Die addisionele byvoeging van Fe2+ aan sulfied magma veroorsaak die kristalisasie van Fe-ryke Mss en verlaag dus die S-konsentrasie van die sulfied smelt. Dit verlaag Pt oplosbaarheid en lei tot die formasie van Py allooie binne-in chromatiete. Ten einde, ontsnap Cu-ryke sulfied smelt deur die onderkant van die chromatiet lae. Die observasies is direk van toepassing op die gemineraliseerde chromatiet riwwe van die Bosveld Kompleks. Ons stel voor dat sulfied magma, potensiaal ingespuit vanuit die mantel saam nuwe inspuitings van silikaat magma, deur die hangende silikaat kumulaat bo chromatiet lae deurgesypel het en ‘n betekenisvolle volume Fe-Mss gekristalliseer het. Chromatiet lae het gefunksioneer as lokvalle vir afwaartsbewegende, ontwikkelde, Cu-, Ni-, en Pt-ryke sulfied vloeistowwe. Dit word ondersteun deur die algemene verskynsel dat chromatiete hoër persentasies van Ni, Cu en Pt relatief teenoor die hangende muur silikaat lae het. Wanneer sulfied smelt in kontak is met chromiet, word dit geforseer om Mss te kristalliseer soos Fe2+ geloogsif word, waarvolgens die smelt se S konsentrasie verder verlaag word. Dit veroorsaak die presipitasie, as Pt allooie, van groot proporsies opgeloste Pt vanuit sulfied smelt. Deur die prosesse te kombineer, kan dit moontlik verduidelik word hoekom chromatiet riwwe in die Bosveld Kompleks Pt/S verhoudings veel hoër is as aanrakende melanoriet lae

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 tumour node metastasis staging at initial presentation.Results. HIV-positive patients were found to be younger than HIV-negative (mean 54.1 (standard deviation 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

Recommendations for the use of endoscopic lung volume reduction in South Africa: Role in the treatment of emphysema

Emphysema is a very common cause of morbidity and mortality in South Africa (SA). Therapeutic options in severe emphysema are limited. Endoscopic lung volume reduction (ELVR) is increasingly being used internationally for the treatment of advanced emphysema in a subset of patients with advanced disease, aiming to obtain the same functional advantages as surgical lung volume reduction while reducing risks and costs. In addition to endobronchial valves, ELVR using endobronchial coils is now available in SA. The high cost of these interventions underscores the need for careful patient selection to best identify those who may or may not benefit from ELVR-related procedures. The Assembly on Interventional Pulmonology of the South African Thoracic Society appointed a committee comprising both local and international experts to extensively review all relevant evidence and provide advice on the use of ELVR in SA based on published evidence, expert opinion and local access to the various devices

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. State-of-the-art 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 resource-constrained environments.Objective. To determine the impact of an electronic CDS for PE on the efficiency of CTPA utilisation in a resource-limited 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 D-dimer test in defining the pre-test 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) prediagnostic algorithm; (ii) post-algorithm, pre-CDS; and (iii) post-CDS.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 non-positive 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 D-dimer, 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