Browsing by Subject "Pulmonology"
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- ItemOpen AccessThe development and validation of a respiratory guideline for nurses in primary care in South Africa(2006) English, René Glynnis; Bateman, Eric D; Bachmann, MaxThe Practical Aproach to Lung Health in South Africa (P ALSA) initiative aims to improve the diagnosis and management of patients with respiratory diseases in primary care. An algorithm-based syndromic guideline integrating common respiratory diseases for nurses was developed after review of a generic respiratory guideline, medical literature, local policies, and qualitative research.
- ItemOpen AccessDiagnostic, prognostic and therapeutic considerations in primary pulmonary hypertension(1987) Chapman, P J; Benatar, Solomon R; Bateman, Eric DThe diagnosis of primary pulmonary hypertension (PPH) and prediction of its course, whether treated or untreated, presents several problems. These are of particular relevance when selection of patients for, and timing of heart-lung transplantation is being considered. I performed a retrospective study on patients with PPH and chronic large vessel thromboembolic pulmonary hypertension (TPH) seen at Groote Schuur Hospital between 1957 and 1985 in an attempt to: 1. Establish the diagnostic and prognostic value of clinical features, lung function tests, cardiac catheterisation, isotope lung scans and, in the PPH group, response to therapy; 2. Review our experience of the effects of treatment with vasodilators and oral anticoagulants, and the results of heart and lung transplantation in the PPH group; 3. Attempt to identify features which could be used to predict prognosis in PPH; and thereby 4. Define criteria for selecting PPH patients whose prognosis could be improved by heart-lung transplantation.
- ItemOpen AccessEarly determinants of lung function in African infants(2016) Gray, Diane Margaret; Zar, Heather; Hall, Graham LChildhood respiratory disease remains a major contributor of morbidity and mortality globally and both paediatric and adult chronic respiratory illness is increasing in prevalence worldwide. This burden of respiratory disease is heaviest in low-middle income countries (LMIC), areas that have a high prevalence of known risk factors for respiratory disease, such us overcrowding, poverty and environmental air pollution. Much chronic respiratory illness has its origin in early life; further low lung function in infancy is associated with later respiratory illness. However, there is limited data on lung function in African infants despite a high prevalence of respiratory disease. Understanding the determinants of infant lung function will improve our understanding of prevention and management of respiratory disease. This thesis aimed to describe lung function in South African infants from six weeks to one year and to investigate the impact of prenatal and early environmental exposures on lung function in infancy. Infants enrolled in the Drakenstein Child Health Study, a multidisciplinary birth cohort study investigating the aetiology and outcome of early life lower respiratory tract infections (LRTI), were included. Seven hundred and forty one infants were enrolled from June 2012 to February 2015. Infants had lung function measured at six (4-10) weeks of age and one year (11-14 months). Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, exhaled nitric oxide, sulphur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal exposures was collected using questionnaires and urine cotinine. Household benzene was measured antenatally. The chapters of the thesis are presented as published manuscripts that describe the establishment of infant lung function for the first time in South Africa and the development of normative lung function in the first year of life. The final chapters investigate the impact of early life exposures, most notably LRTI, on lung function at six weeks and one year. The thesis concludes that infant lung function testing is feasible in a community setting in 11 a LMIC like South Africa. Size, gender and ethnicity are important determinants of lung function. Lung function of South African infants is not well predicted by European reference equations, highlighting the importance of using population specific reference data when interpreting lung function tests. The study identifies several factors including maternal smoking, maternal alcohol and household benzene exposure during pregnancy, associated with altered early lung function. In addition tracking of lung function in the first year of life is described in this cohort of African infants living in a high respiratory disease burden setting. The study identifies risk factors for impaired lung function at one year independent of low baseline lung function: LRTI, household smoke exposure and infant nutrition, factors amenable to public health intervention. Given the fact that infant lung function tracks into later life and plays a role in chronic respiratory disease, preventing respiratory illness in young children, reducing exposure to environmental tobacco and maximising nutrition are key priorities in the strengthening of child respiratory health. Long-term study of lung function and respiratory disease in these infants is a priority in order to develop new strategies to strengthen child health.
- ItemOpen AccessEarly sequelae of post COVID-19 lung disease in patients who were mechanically ventilated for severe COVID-19 pneumonia(2023) Singh, Nevadna; Van Zyl-Smit, RichardIntroduction: COVID-19 resulted in an unprecedented worldwide spike in hospital and ICU admissions; predominantly for adult respiratory distress syndrome (ARDS). Survival rates for patients requiring mechanical ventilation in Cape Town during the waves driven by the ancestral strain and beta variant were approximately 30% during the first 3 waves of the pandemic. However, post-ICU admission sequelae and recovery trajectory in sub-Saharan Africa remain unknown. Methods: We systematically evaluated a cohort of COVID-19 ICU survivors at three months following hospital discharge. A retrospective single-centre study enrolled all COVID-19 pneumonia patients who were admitted to ICU for mechanical ventilation and followed up at the post-COVID-19 Lung Disease Clinic between 1 July 2020 and 30 December 2021. Results: A total of 26 patients were evaluated at 3 months after discharge from hospital following mechanical ventilation: 53% were male and 81% had at least one co-morbidity. Diabetes and hypertension were present in 42% and 54% of patients respectively. Persistent dyspnoea (89%) and fatigue (54%) were the most common post-COVID-19 symptoms. Median FEV1 and FVC were 73% (IQR 65-83) and 71% (IQR 61-77) of predicted values respectively, whilst median DLCO was 59% (IQR 41- 70) of predicted values. Abnormalities were confirmed in all patients (24/26) who underwent high resolution computer tomography (HRCT) of the chest, with ground glass opacities (46%) and interstitial thickening (58%) being most common. No significant risk factors for post-COVID-19 impairment were identified. Conclusion: At 3 months after hospitalization, patients who received mechanical ventilation for COVID-19 pneumonia frequently reported ongoing symptoms. Lung function was moderately impaired with a disproportionate reduction in DLCO, and radiographic abnormalities were common. Long term follow up is required to determine the natural history post severe-COVID-19 lung disease.
- ItemOpen AccessIndoor air pollution and environmental tobacco smoke exposure in a South African birth cohort study(2018) Vanker, Aneesa; Zar, Heather J; Gie, Robert Pmiddleincome countries (LMIC) and a major reason for health care visits and hospitalisation. Environmental exposures to indoor air pollution (IAP) or tobacco smoke are important risk factors for childhood respiratory disease. Despite increased electrification, many communities in LMIC rely on alternate fuel sources for household cooking or heating. The impact of antenatal or postnatal exposures on early childhood respiratory disease has not been comprehensively studied in LMIC especially in Africa. The aim of this work was to investigate the impact of IAP and environmental tobacco smoke (ETS) exposure on child health and early-life respiratory disease in the Drakenstein Child Health Study (DCHS), a South African birth cohort study. The DCHS investigates the epidemiology and impact of early-life exposures on child health including lung disease. The study is set in a peri-urban poor community in the Western Cape, South Africa. Pregnant women were enrolled from two public primary healthcare clinics, Mbekweni (serving a predominantly black African population) and Newman (predominantly mixed-ancestry population) and 1000 mother-infant pairs longitudinally followed from birth through 1 year of life. The thesis chapters are presented as published manuscripts that describe IAP and ETS exposure in the 2 communities in the DCHS cohort from the antenatal period and the impact of these exposure on child health and lung diseases, LRTI and wheezing illness in the first year of life. To measure exposures comprehensively, two home visits, one in the antenatal period (third trimester) and the second postnatally (between 4 and 6 months of the infant’s life), were conducted to assess the home environment and to measure the most common indoor air pollutants and by-products of combustion. Devices placed in participants’ homes measured exposure to particulate matter (PM10), carbon monoxide (CO), nitrogen dioxide (NO2), sulphur dioxide (SO2) and volatile organic compounds (VOC). Maternal and infant urine cotinine measures were used to validate self-reported tobacco smoking and exposure. Study staff trained in recognition of LRTI or wheeze documented all episodes, which were categorised according to WHO case definition criteria. Exposure to IAP was comprehensively assessed in over 800 homes antenatally and postnatally providing important South African data on IAP and potential sources of exposure. Tobacco smoke exposure was assessed longitdunially by maternal self-report using validated scales and by measurement of urine cotinine in mothers and infants. Tobacco smoke exposure was found to be highly prevalent with a smoking prevalence of >50% in mixedancestry mothers. Alarmingly, 18% of infants were born with urine cotinine levels in keeping with active smoking, while a further 30% had levels indicating passive smoke exposure. Key findings were despite 92% of homes reporting access to electricity, there was still a reliance on cheaper alternate fuels. Tobacco smoking prevalence amongst pregnant women was high (32%), as was household exposure to tobacco smoke (44%). ETS exposure was associated with low birth weight and antenatal IAP or ETS exposure was significantly associated with increased LRTI. ETS exposure was also associated with wheezing illnesses. A novel finding was that antenatal exposure to toluene, a volatile organic compound, was associated with severe LRTI and hospitalisation. The timing of environmental exposures on the subsequent development of LRTI in infancy has not been well described. An important finding was that antenatal exposures were the main risk factors associated with LRTI, with maternal smoking in pregnancy or PM10 exposure most strongly associated with LRTI. Wheezing illness was associated with both antenatal and postnatal maternal smoking and antenatal maternal smoke exposure and postnatal household member smoking. Both IAP and ETS exposure impacted on both maternal and infant nasopharyngeal bacterial carriage which may be a precursor to the development of LRTI. Environmental exposures therefore had a substantial impact on child health and on LRTI and wheezing illness. The effect on LRTI of antenatal compared with postnatal exposure suggests an in utero developmental lung effect. This study highlights antenatal and early life as a critical period for lung development. Urgent and effective smoking cessation programmes targeting women of child bearing age as well as public health interventions to reduce IAP are required. Woman of childbearing age, pregnant women and children in poor communities represent vulnerable populations at risk for long-term health effects of these exposures.
- ItemRestrictedMicrobiological, genomic and transcriptomic analyses of human tuberculosis lung cavities(2016) Lenders, Laura Mary; Dheda, Keertan; Warren, Rob; Davids, MalikaBACKGROUND: Tuberculosis (TB) remains out of control globally. Recent promising vaccine candidates have failed in clinical trials and host immunity in the lung remains poorly understood. Pathogenesis of pulmonary cavitation, the basis of TB transmission, is poorly understood. The degree of heteroresistance in the human lung remains unclear. METHODOLOGY: Multi- and extensively drug-resistant TB (MDR- and XDR-TB) patients scheduled for therapeutic lung resection surgery in Cape Town were prospectively recruited. Biopsies were obtained from specific positions in and around cavities. Drug-susceptibility testing, strain-type determination, whole-genome sequencing, and whole-transcriptome shotgun sequencing was conducted. RESULTS: Samples were obtained from 2 MDR-TB, 1 pre-XDR-TB and 12 XDR-TB patients, and 10 non- TB controls. There was considerable heterogeneity between sputum and the cavity with respect to genomic and phenotypic profiles of several drugs including ethambutol, moxifloxacin and paraaminosalicylic acid. An anatomically distinct whole-transcriptome-based pathophysiological map of TB cavities was constructed. RNA sequence reads, of which 31% were splice variants, mapped to 19,049 annotated human genes. In peri-cavitary normal-appearing tissue only 33% of pathways showed significant expression change, despite having a similar bacillary burden to diseased tissue. However, in the cavity wall 72% of pathways showed high-intensity increased expression. By contrast, in the cavity center with a high bacillary burden, 53% of these pathways were massively downregulated, differing from airways and sputum. In particular, several neuroendocrine pathways (dopamine, glutamate, synaptic long-term signalling) were significantly downregulated together with those encoding for calcium, retinoic acid-inducible gene-1, and other pathogen-recognition receptors. However, genes encoding for eukaryotic initiation factor-2, triggering receptor expressed on myeloid cell-1 and peroxisome proliferator activated receptor gamma-signalling, amongst others, were upregulated. CONCLUSION: Heterogeneity in genomic and phenotypic profiles within different parts of the cavity and sputum suggests dynamic responses of mycobacterial populations, likely, under the selective pressure of treatment, which has implications for the interpretation and development of TB-specific diagnostic tests. These data may also have important implications for understanding the pathogenesis of failed host immunity and have uncovered several, hitherto, unrecognized pathways and targets that may be useful for the design of vaccines, host-directed therapies, and transmission prevention.
- ItemOpen AccessNovel and newer nucleic acid amplification tests for the diagnosis of TB(2016) Matinyenya, Brian; Dheda, Keertan; Theron, GrantBackground: Current tools for TB diagnosis have suboptimal accuracy, perform poorly in diagnosing extra-pulmonary TB, and are not point of care; hence results have a slow turn-around time. Objective: This project evaluated the diagnostic accuracy of the promising novel loop mediated isothermal amplification (LAMP) assay on sputum, and that of the semi-automated Xpert MTB/RIF (Xpert) test on non-sputum specimens (bronchoalveolar lavage fluid [BALF], tracheal aspirates, and cerebrospinal fluid [CSF]) from South African patients with suspected TB (the accuracy of Xpert using these fluids was unknown at the time this work was performed). Methodology: Biological samples (sputum, tracheal aspirates, BALF, or CSF) were collected from patients with suspected TB. Liquid culture served as the reference standard for the diagnosis of definite TB. Accuracy was evaluated according to HIV and smear microscopy status, where appropriate. The relationship between test performance and bacterial load (culture time-to-positivity [TTP]) was also compared. For the evaluation of LAMP, 2 spot sputa of approximately 4 ml were collected from 301 patients (60 μl of sputum was used for the assay). For the evaluation of Xpert on BALF, 152 patients who were sputum scarce or smear-negative were recruited (1 ml of the BALF aliquot or a re-suspended pellet from 10 ml BALF was used). For the evaluation of Xpert on tracheal aspirates, 120 tracheal aspirates from patients enrolled in the intensive care unit (ICU) were tested. For the evaluation of Xpert on CSF, 235 patients with suspected TBM had a lumbar puncture with 1 ml of CSF or where available a re-suspended pellet from 3 ml of CSF evaluated using Xpert.
- ItemOpen AccessThe pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis(Biomed Central Ltd, 2007) Lala, Sanjay; Dheda, Keertan; Chang, Jung-Su; Huggett, Jim; Kim, Louise; Johnson, Margaret; Rook, Graham; Keshav, Satish; Zumla, AlimuddinBACKGROUND:NOD2, an intracellular pathogen recognition sensor, modulates innate defences to muropeptides derived from various bacterial species, including Mycobacterium tuberculosis (MTB). Experimentally, NOD2 attenuates two key putative mycobactericidal mechanisms. TNF-alpha synthesis is markedly reduced in MTB-antigen stimulated-mononuclear cells expressing mutant NOD2 proteins. NOD2 agonists also induce resistance to apoptosis, and may thus facilitate the survival of MTB in infected macrophages. To further define a role for NOD2 in disease pathogenesis, we analysed NOD2 transcriptional responses in pulmonary leucocytes and mononuclear cells harvested from patients with pulmonary tuberculosis (PTB). METHODS: We analysed NOD2 mRNA expression by real-time polymerase chain-reaction in alveolar lavage cells obtained from 15 patients with pulmonary tuberculosis and their matched controls. We compared NOD2 transcriptional responses, in peripheral leucocytes, before and after anti-tuberculous treatment in 10 patients. In vitro, we measured NOD2 mRNA levels in MTB-antigen stimulated-mononuclear cells. RESULTS: No significant differences in NOD2 transcriptional responses were detected in patients and controls. In some patients, however, NOD2 expression was markedly increased and correlated with toll-like-receptor 2 and 4 expression. In whole blood, NOD2 mRNA levels increased significantly after completion of anti-tuberculosis treatment. NOD2 expression levels did not change significantly in mononuclear cells stimulated with mycobacterial antigens in vitro. CONCLUSION: There are no characteristic NOD2 transcriptional responses in PTB. Nonetheless, the increased levels of NOD2 expression in some patients with severe tuberculosis, and the increases in expression levels within peripheral leucocytes following treatment merit further studies in selected patient and control populations.
- ItemOpen AccessThe relationship between clinical trial participation and inhaler technique errors in asthma and COPD patients(2020) Perumal, Rubeshan; Van Zyl-Smit, RichardBackground Incorrect inhaler use is associated with poorer health outcomes, reduced quality of life, and higher healthcare utilisation in patients with asthma and COPD. Method We performed an observational study of pressurized metered-dose inhaler technique in patients with asthma or COPD. Patients were assessed using a six-point inhaler checklist to identify common critical inhaler technique errors. An inadequate inhaler technique was defined as the presence of one or more critical errors. A multivariate logistic regression model was used to determine the odds of an inadequate inhaler technique. Results During the 14-month study period, 357 patients were enrolled. At least one critical error was executed by 66.7% of participants, and 24.9% made four or more critical errors. The most common errors were: failure to exhale completely prior to pMDI activation and inhalation (49.6%), failure to perform a slow, deep inhalation following device activation (48.7%), and failure to perform a breathhold at the end of inspiration (47.3%). The risk of a critical error was higher in COPD patients (aOR 2.25, 95%CI 1.13 – 4.47). Prior training reduced error risk specifically when trained by a doctor (aOR 0.08, 95% CI 0.1 – 0.57) or a pharmacist (aOR 0.02, 95% CI 0.01 – 0.26) compared to those with no training. Previous clinical trial participation significantly reduced error risk and rate:< 3 trials (aOR 0.35, 95% CI 0.19 – 0.66) and ≥3 trials (aOR 0.17, 95% CI 0.07 – 0.42). The rate of critical errors was not significantly associated with age, sex, or prior pMDI experience. Conclusion This study found a high rate of critical inhaler technique errors in a mixed population of asthma and COPD patients; however, prior training and in particular, multiple previous clinical trial participation significantly reduced the risk of errors.