C F N Koegelenberg

Tuberculous pleural effusions: advances and controversies

On a global scale, tuberculosis (TB) remains one of the most frequent causes of pleural effusions. Our understanding of the pathogenesis of the disease has evolved and what was once thought to be an effusion as a result of a pure delayed hypersensitivity reaction is now believed to be the consequence of direct infection of the pleural space with a cascade of events including an immunological response. Pulmonary involvement is more common than previously believed and induced sputum, which is grossly underutilised, can be diagnostic in approximately 50%. The gold standard for the diagnosis of tuberculous pleuritis remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli (AFB). In high burden settings, however, the diagnosis is frequently inferred in patients who present with a lymphocytic predominant exudate and a high adenosine deaminase (ADA) level, which is a valuable adjunct in the diagnostic evaluation. ADA is generally readily accessible, and together with lymphocyte predominance justifies treatment initiation in patients with a high pre-test probability. Still, false-negative and false-positive results remain an issue. When adding closed pleural biopsy to ADA and lymphocyte count, diagnostic accuracy approaches that of thoracoscopy. The role of other biomarkers is less well described. Early pleural drainage may have a role in selected cases, but more research is required to validate its use and to define the subpopulation that may benefit from such interventions.

The utility of ultrasound-guided thoracentesis and pleural biopsy in undiagnosed pleural exudates

We assessed the utility of ultrasound to guide the selection of closed pleural biopsy technique and site and to assess the respective contributions of repeat thoracentesis and closed pleural biopsy in 100 consecutive patients with undiagnosed pleural exudates. Thoracentesis was more likely to be diagnostic in TB than malignancy (77.8% vs 31.0%, p<0.001). The addition of ultrasound-guided biopsy increased the combined yield for all diagnoses from 48.0% to 90.0% (p<0.001), for malignancy from 31.0% to 89.7% (p<0.001) and for TB from 77.8% to 88.9% (p=0.688). Our findings suggest that this minimally invasive approach has a high diagnostic yield.

Time for the Global Rollout of Endoscopic Lung Volume Reduction

Chronic obstructive pulmonary disease remains one of the most common causes of morbidity and mortality globally. The disease is generally managed with pharmacotherapy, as well as guidance about smoking cessation and pulmonary rehabilitation. Endoscopic lung volume reduction (ELVR) has been proposed for the treatment of advanced emphysema, with the aim of obtaining the same clinical and functional advantages of surgical lung volume reduction whilst potentially reducing risks and costs. There is a growing body of evidence that certain well-defined sub-groups of patients with advanced emphysema may benefit from ELVR, provided the selection criteria are met and a systematic approach is followed. ELVR devices, particularly unidirectional valves and coils, are currently being rolled out to many countries outside of the USA and Europe, although very few centres currently have the capacity to correctly evaluate and provide ELVR to prospective candidates. The high cost of these interventions underpins the need for careful patient selection to best identify those who may or may not benefit from ELVR-related procedures. The aim of this review is to provide the practicing pulmonologist with an overview of the practical aspects and current evidence for the use of the various techniques available, and to suggest an evidence-based approach for the appropriate use of these devices, particularly in emerging markets, where there should be a drive to develop and equip key specialised ELVR units.

Direct comparison of liquid-based and smear-based cytology with and without rapid on-site evaluation for fine needle aspirates of thoracic tumors.

Liquid‐based cytology (LBC) and rapid on‐site evaluation (ROSE) are proposed to improve the quality of fine needle aspirates (FNA) and their diagnostic yield compared with conventional smear cytology (CSC). This prospective study directly compared outcomes of sonar‐guided FNA of thoracic tumors supported by LBC, CSC, or CSC with ROSE.

Adenocarcinoma the most common cell type in patients presenting with primary lung cancer in the Western Cape

2We found that adenocarcinoma is now the most common histological subtype of primary lung cancer diagnosed in the Western Cape and that almost 90% of all patients with non-small cell lung cancer have advanced local or metastatic disease at the time of diagnosis. ‘Lung cancer’ denotes cancer arising in the airways and pulmonary parenchyma. Its histopathological designation is based on the World Health Organization classification system, with 4 cell types responsible for most deaths: adenocarcinoma (including bronchoalveolar carcinoma), squamous cell carcinoma, large cell (undifferentiated) carcinoma and small cell carcinoma. 3 Carcinoid tumours and other rare cell types complete the list of cell types. An interesting phenomenon in the developed world over the last two decades has been the relative increase in the diagnosis of adenocarcinoma which has replaced squamous cell carcinoma as the most frequent histological subtype. 4 Many explanations for this well-documented phenomenon have been suggested. There are few current South African data regarding the relative incidence of the various cell types. The latest National Cancer Registry (NCR) report is from 2001, and contains no data on the relative incidence of the lung cancer cell types. 5 Moreover, published and unpublished data from the 1980s suggested that more than 50 - 60% of all lung cancers were squamous cell carcinomas. 6

Recommendations for the use of bronchial thermoplasty in the management of severe asthma

There are approximately 3 million asthma suffers in South Africa, and the national death rate is ranked as one of the highest in the world. Approximately 5% have severe asthma (uncontrolled despite being adherent on maximal and optimised therapy). Such uncontrolled asthma is associated with high healthcare expenditure and may require treatment with anti-IgE and/or systemic corticosteroids, in addition to inhaler therapy and oral agents. These treatments may be costly, and those such as oral corticosteroids may have potential serious adverse events. There is therefore a need for more effective, affordable and safe therapies for asthma. A new modality of treatment, bronchial thermoplasty (BT), has recently been developed and approved for the treatment of severe asthma. BT involves delivering radio frequency-generated thermal energy to the airways, with the goal of reducing airway-specific smooth-muscle mass. Several clinical studies have confirmed that BT is effective and safe, that it improves control and quality of life in patients whose asthma remains severe despite optimal medical therapy, and that the beneficial effects are sustained for at least 5 years. We provide recommendations for the management of severe asthma, with an emphasis on the role of BT, and endorse the use of BT in patients with severe persistent asthma who remain uncontrolled despite optimal medical therapy as outlined in steps 4 and 5 of the British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN), UK National Institute of Clinical Excellence (NICE) and Global Initiative for Asthma (GINA) guidelines. We outline the context in which BT should be used, how it works and associated potential adverse events and contraindications, and also review unanswered questions and controversies.

The diagnostic accuracy of integrated positron emission tomography/computed tomography in the evaluation of pulmonary mass lesions in a tuberculosis-endemic area

BACKGROUND Integrated positron emission tomography/computed tomography (PET-CT) is a well-validated modality for assessing pulmonary mass lesions and specifically for estimating risk of malignancy. Tuberculosis (TB) is known to cause false-positive PET-CT findings. OBJECTIVE To investigate the utility of PET-CT in the evaluation of pulmonary mass lesions and nodules in a high TB prevalence setting. METHODS All patients referred for the evaluation of a solitary pulmonary nodule or mass and who underwent PET-CT scanning over a 3-year period were included. The PET-CT findings, including maximum standardised uptake value (SUVmax), were compared with the gold standard (tissue or microbiological diagnosis). The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy for malignant disease were calculated according to the SUVmax cut-off of 2.5 and a proposed cut-off obtained from a receiver operating characteristic (ROC) curve. RESULTS Forty-nine patients (mean (standard deviation) age 60.1 (10.2) years; 29 males) were included, of whom 30 had malignancy. Using an SUVmax cut-off of 2.5, PET-CT had a sensitivity, specificity, positive and negative predictive value and diagnostic accuracy for malignancy of 93.3%, 36.8%, 70.0%, 77.8% and 71.4%, respectively. After a ROC curve analysis, a suggested SUVmax cut-off of 5.0 improved the specificity to 78.9% and the diagnostic accuracy to 86.7%, with a small reduction in sensitivity to 90.0%. CONCLUSIONS The diagnostic accuracy of PET-CT in the evaluation of pulmonary mass lesions using the conventional SUVmax cut-off of 2.5 was reduced in a TB-endemic area. An SUVmax cut-off of 5.0 has a higher specificity and diagnostic accuracy for malignancy, with a comparable sensitivity.

Transbronchial fine needle aspiration biopsy and rapid on-site evaluation in the setting of superior vena cava syndrome

There is a paucity of prospective data on flexible bronchoscopy with rapid on‐site evaluation (ROSE) in the setting of superior vena cava (SVC) syndrome. The aims of this prospective study were to assess the diagnostic yield and safety of these investigations and specifically to evaluate the role of ROSE in limiting the need for tissue biopsies. Over a 5‐year period 48 patients (57.4 ± 9.7 years) with SVC syndrome secondary to intrathoracic tumors underwent flexible bronchoscopy with TBNA and ROSE. Endobronchial Forceps biopsy was reserved for visible endobronchial tumors with no on‐site confirmation of diagnostic material. ROSE confirmed diagnostic material in 41 cases (85.4%), and in only one of the remaining cases did the addition of a forceps biopsy increase the diagnostic yield (overall diagnostic yield of 87.5%). No serious complications were noted. The final diagnoses made included nonsmall lung cancer (n = 27), small cell lung cancer (n = 16), and metastatic carcinoma (n = 3). Two undiagnosed cases died of suspected advanced neoplasms (unknown primary tumors). We conclude that TBNA has a high diagnostic yield and is safe in the setting of SVC syndrome. With the addition of ROSE, tissue biopsy is required in the minority of cases. Diagn. Cytopathol. 2013;41:324–329.

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 >1000 ng/ml were associated with QT and QRS prolongation and convulsions. However, no single parameter predicted non-survival. The overall mortality of TCA overdose was very low. Our findings should encourage clinicians to offer medical care including ICU admission, if necessary, to patients with TCA overdose.

Validation of a severity-of-illness score in HIV-positive patients requiring intensive care unit admission for mechanical ventilation

There is a paucity of high-quality evidence on the predictors of mortality of HIV-positive patients admitted to the intensive care unit (ICU) in high HIV-prevalence settings. In a recent study we found that the ICU mortality of mechanically ventilated HIV-positive patients was around 40%.1 Overt acquired immune deficiency syndrome (AIDS) and a higher Acute Physiology and Chronic Health Evaluation II score independently predicted ICU mortality. We subsequently performed a post-hoc analysis of our data in order to develop and retrospectively validate a simple severity-of-illness score for potential use in patients with HIV requiring mechanical ventilation. The presence of (i) septic shock and (ii) renal impairment …