South African Thoracic Society position statement on the management of non-cystic fibrosis bronchiectasis in adults: 2023.

Background: Bronchiectasis is a chronic lung disorder that affects the lives of many South Africans. Post-tuberculosis (TB) bronchiectasis is an important complication of previous pulmonary TB and a common cause of bronchiectasis in South Africa (SA). No previous statements on the management of bronchiectasis in SA have been published. Objectives: To provide a position statement that will act as a template for the management of adult patients with bronchiectasis in SA. Methods: The South African Thoracic Society appointed an editorial committee to compile a position statement on the management of adult non-cystic fibrosis (CF) bronchiectasis in SA. Results: A position statement addressing the management of non-CF bronchiectasis in adults in SA was compiled. This position statement covers the epidemiology, aetiology, diagnosis, investigations and various aspects of management of adult patients with non-CF bronchiectasis in SA. Conclusion: Bronchiectasis has largely been a neglected lung condition, but new research has improved the outlook for patients. Collaboration between interprofessional team members in patient management is important. In SA, more research into the epidemiology of bronchiectasis, especially post-TB bronchiectasis and HIV-associated bronchiectasis, is required. Abstract: The South African Thoracic Society mandated a multidisciplinary team of healthcare providers to compile a position statement on the management of non-cystic fibrosis bronchiectasis in South Africa (SA). International guidelines on the management of bronchiectasis were reviewed and used as a basis from which the current position statement was compiled. This is the first position statement on the management of adult non-cystic fibrosis bronchiectasis in SA. A description of the epidemiology and aetiology of bronchiectasis is provided, as well as guidance on its diagnosis and management. The position statement provides guidance on the management of bronchiectasis to healthcare providers, policymakers and regulatory authorities.

Lung microbiome of stable and exacerbated COPD patients in Tshwane, South Africa.

Chronic obstructive pulmonary disease (COPD) is characterised by the occurrence of exacerbations triggered by infections. The aim of this study was to determine the composition of the lung microbiome and lung virome in patients with COPD in an African setting and to compare their composition between the stable and exacerbated states. Twenty-four adult COPD patients were recruited from three hospitals. Sputum was collected and bacterial DNA was extracted. Targeted metagenomics was performed to determine the microbiome composition. Viral DNA and RNA were extracted from selected samples followed by cDNA conversion. Shotgun metagenomics sequencing was performed on pooled DNA and RNA. The most abundant phyla across all samples were Firmicutes and Proteobacteria. The following genera were most prevalent: Haemophilus and Streptococcus. There were no considerable differences for alpha and beta diversity measures between the disease states. However, a difference in the abundances between disease states was observed for: (i) Serratia (3% lower abundance in exacerbated state), (ii) Granulicatella (2.2% higher abundance in exacerbated state), (iii) Haemophilus (5.7% higher abundance in exacerbated state) and (iv) Veillonella (2.5% higher abundance in exacerbated state). Virome analysis showed a high abundance of the BeAn 58058 virus, a member of the Poxviridae family, in all six samples (90% to 94%). This study is among the first to report lung microbiome composition in COPD patients from Africa. In this small sample set, no differences in alpha or beta diversity between stable and exacerbated disease state was observed, but an unexpectedly high frequency of BeAn 58058 virus was observed. These observations highlight the need for further research of the lung microbiome of COPD patients in African settings.

Comparison of targeted metagenomics and IS-Pro methods for analysing the lung microbiome.

BACKGROUND: Targeted metagenomics and IS-Pro method are two of the many methods that have been used to study the microbiome. The two methods target different regions of the 16 S rRNA gene. The aim of this study was to compare targeted metagenomics and IS-Pro methods for the ability to discern the microbial composition of the lung microbiome of COPD patients. METHODS: Spontaneously expectorated sputum specimens were collected from COPD patients. Bacterial DNA was extracted and used for targeted metagenomics and IS-Pro method. The analysis was performed using QIIME2 (targeted metagenomics) and IS-Pro software (IS-Pro method). Additionally, a laboratory cost per isolate and time analysis was performed for each method. RESULTS: Statistically significant differences were observed in alpha diversity when targeted metagenomics and IS-Pro methods' data were compared using the Shannon diversity measure (p-value = 0.0006) but not with the Simpson diversity measure (p-value = 0.84). Distinct clusters with no overlap between the two technologies were observed for beta diversity. Targeted metagenomics had a lower relative abundance of phyla, such as the Proteobacteria, and higher relative abundance of phyla, such as Firmicutes when compared to the IS-Pro method. Haemophilus, Prevotella and Streptococcus were most prevalent genera across both methods. Targeted metagenomics classified 23 % (144/631) of OTUs to a species level, whereas IS-Pro method classified 86 % (55/64) of OTUs to a species level. However, unclassified OTUs accounted for a higher relative abundance when using the IS-Pro method (35 %) compared to targeted metagenomics (5 %). The two methods performed comparably in terms of cost and time; however, the IS-Pro method was more user-friendly. CONCLUSIONS: It is essential to understand the value of different methods for characterisation of the microbiome. Targeted metagenomics and IS-Pro methods showed differences in ability in identifying and characterising OTUs, diversity and microbial composition of the lung microbiome. The IS-Pro method might miss relevant species and could inflate the abundance of Proteobacteria. However, the IS-Pro kit identified most of the important lung pathogens, such as Burkholderia and Pseudomonas and may work in a more diagnostics-orientated setting. Both methods were comparable in terms of cost and time; however, the IS-Pro method was easier to use.

Drug-resistant tuberculosis clinical trials: proposed core research definitions in adults.

Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for the first time in decades, new drugs for the treatment of this disease have been developed. These new drugs have prompted strengthened efforts in DR-TB clinical trials research, and there are now multiple ongoing and planned DR-TB clinical trials. To facilitate comparability and maximise policy impact, a common set of core research definitions is needed, and this paper presents a core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work. To elaborate these definitions, a search of clinical trials registries, published manuscripts and conference proceedings was undertaken to identify groups conducting trials of new regimens for the treatment of DR-TB. Individuals from these groups developed the core set of definitions presented here. Further work is needed to validate and assess the utility of these definitions but they represent an important first step to ensure there is comparability in clinical trials on multidrug-resistant TB.

An unusual cause of an anterior mediastinal mass.

Mesothelioma is a rare tumour and its radiological growth pattern varies. We report the case of a biopsy proven Malignant Pleural Mesothelioma (MPM) presenting as an anterior mediastinal mass in a platinum miner. The prognosis for this aggressive tumour remains poor, despite combination treatment modalities.

Prognostic factors in severe community-acquired pneumonia in patients without co-morbid illness.

OBJECTIVES: We wished to determine the prognostic factors and the impact of initial empirical antibiotic therapy on the outcome of severe community-acquired pneumonia in patients without underlying co-morbid illness. METHODOLOGY: This is a retrospective record review of consecutive patients with severe community-acquired pneumonia who were divided into those with and without underlying co-morbid illness. RESULTS: There were 182 patients including 112 primary (no co-morbid illness) and 70 secondary (underlying co-morbid illness) pneumonias. The overall mortality was 41.8% and there were no differences in APACHE II score or mortality when comparing cases with primary (37.5%) and secondary infections (48.6%). The mortality was significantly higher in patients with negative microbiology. Univariate analysis identified a number of parameters and various antibiotic regimens, which appeared to be associated with a significantly poorer outcome. On multivariate analysis multilobar pulmonary consolidation, need for mechanical ventilation, inotropes and dialysis were documented to be independent predictors of mortality. Only in their absence could different antibiotic regimens be shown to have an apparent impact on outcome and further analysis suggested that the reason for these differences related predominantly to differences in the severity of the infection. CONCLUSIONS: Markers of disease severity appear to be the most important predictors of outcome in patients with severe community-acquired pneumonia.

The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation.

Endotracheal tube colonization in patients undergoing mechanical ventilation was investigated. In the first part of this prospective study, the airway access tube was examined for the presence of secretions, airway obstruction and bacterial colonization, in cases undergoing extubation or tube change. In the second part of the study, the sequence of oropharyngeal, gastric, respiratory tract and endotracheal tube colonization was investigated by sequential swabbing at each site twice daily for 5 days in consecutive noninfected patients. In the first part, it was noted that all airway access tubes of cases undergoing extubation had secretions lining the interior of the distal third of the tube which were shown on scanning electron microscopy to be a biofilm. Gram-negative micro-organisms were isolated from these secretions in all but three cases. In the second part, it was noted that the sequence of colonization in patients undergoing mechanical ventilation was the oropharynx (36 h), the stomach (3660 h), the lower respiratory tract (60-84 h), and thereafter the endotracheal tube (60-96 h). Nosocomial pneumonia occurred in 13 patients and in eight cases identical organisms were noted in lower respiratory tract secretions and in secretions lining the interior of the endotracheal tube. The endotracheal tube of patients undergoing mechanical ventilation becomes colonized rapidly with micro-organisms commonly associated with nosocomial pneumonia, and which may represent a persistent source of organisms causing such infections.

Effect of rolipram and dibutyryl cyclic AMP on resequestration of cytosolic calcium in FMLP-activated human neutrophils.

1. We have investigated the effects of the selective phosphodiesterase (PDE) type 4 inhibitor, rolipram (0.01-1 microM) on cytosolic Ca2+ fluxes in FMLP-activated human neutrophils, as well as on superoxide production by, and release of elastase from, these cells. 2. Cytosolic Ca2+ fluxes were measured by use of fura-2 spectrofluorimetry in combination with a radiometric procedure that enables distinction between net efflux and influx of the cation. Superoxide production and elastase release were measured by lucigenin-enhanced chemiluminescence and a colorimetric procedure, respectively. 3. Pretreatment of neutrophils with rolipram did not affect the FMLP-activated release of Ca2+ from intracellular stores, but was associated with dose-related acceleration of the rate of decline in fura-2 fluorescence and with decreased efflux, as well as store-operated influx of 45Ca2+, indicative of enhancement of resequestration of the cation by the endo-membrane Ca2+-ATPase. 4. Inhibition of superoxide production and elastase release was observed at concentrations of rolipram which accelerated the clearance of Ca2+ from the cytosol of FMLP-activated neutrophils. 5. These effects of rolipram on FMLP-activated Ca2+ fluxes, superoxide generation and elastase release were mimicked by pretreatment of neutrophils with dibutyryl cyclic AMP (0.5-4 mM), while theophylline (10-150 microM), a non-specific PDE inhibitor, as well as the beta2-agonist, salbutamol, were less effective. 6. We conclude that rolipram deactivates FMLP-stimulated human neutrophils by enhancement of cyclic AMP-dependent resequestration of cytosolic Ca2+.

Calcium efflux and influx in f-met-leu-phe (fMLP)-activated human neutrophils are chronologically distinct events.

The kinetics of efflux of calcium mobilized from intracellular stores following activation of human neutrophils with the synthetic chemotactic tripeptide, fMLP (1 microM), as well as that of the subsequent store-operated influx of this cation, has been measured by radiometric procedures using 45Ca. These procedures enabled distinction between net efflux and influx of 45Ca. Preincubation of neutrophils in medium containing 45Ca as the sole source of Ca2+, followed by activation with fMLP, resulted in a rapid efflux of the cation, which coincided with its release from intracellular stores. Efflux terminated at approximately 30 s after addition of fMLP to neutrophils and resulted in the loss of 42 +/- 3% (P < 0.005) of cell-associated 45Ca. Net influx of 45Ca, which was insensitive to the voltage-dependent Ca2+ channel blockading agent, verapamil (20 microM), could only be detected at 30-60 s after the addition of fMLP to neutrophils, and proceeded for about 5 min, resulting in intracellular concentrations of Ca2+ which were 27 +/- 3% (P<0.05) higher than preactivation levels. These results demonstrate that the efflux of cytoplasmic Ca2+ mobilized from intracellular stores during activation of neutrophils by fMLP, and the subsequent influx of extracellular Ca2+ to replete these stores, are chronologically distinct events in fMLP-activated neutrophils.

Cryptococcosis: an unusual cause of endobronchial obstruction.

We report the case of a 43 year old male patient, with normal immune function, who presented with right middle and lower lobe collapse. At bronchoscopy, a white lobulated lesion was seen, completely obstructing the origin of bronchus intermedius. Bronchial washings and biopsy of the lesion demonstrated cryptococcal organisms. The patient responded clinically and radiologically to amphotericin B and flucytosine; however, repeat bronchoscopy revealed only partial resolution of the endobronchial lesion.

Factors associated with airway colonisation and invasion due to Klebsiella spp.

The clinical significance of a heavy growth of Klebsiella spp. in sputum was studied in 54 patients. All but 3 patients had significant factors potentially associated with respiratory tract colonisation or invasion. Risk factors identified for colonisation of the airway and for invasive disease were similar. Patients with community-acquired Klebsiella infections were more likely to have underlying chronic respiratory diseases. Prior antibiotic use was a risk factor for nosocomial infections which occurred more commonly with antibiotic-resistant organisms. The most common diagnoses were airway colonisation, acute community-acquired chest infections, and nosocomial chest infections. Primary acute community-acquired pneumonia was uncommon. The sensitivity and specificity of the sputum Gram stain (in the setting of positive sputum cultures) in suggesting the presence of invasive disease due to Klebsiella spp. were 42% and 69% respectively.

Does primary Streptococcus viridans pneumonia exist?

In 4 adult black patients admitted to an urban general hospital with community-acquired pneumonia, Streptococcus viridans alone was isolated from blood culture (first subculture), in the absence of any other positive microbiological finding. Sputum examination by Gram staining and culture in 3 cases was reported as negative. Echocardiography was performed in 3 cases and was normal, without evidence of endocarditis. The clinical course of illness in the 4 patients is described. The chest radiograph showed a segmental or subsegmental consolidation in all cases; this appeared 'mass-like' in 2 patients. Viridans streptococci may be a more important, if still uncommon, cause of community-acquired pneumonia than previously suspected. The organism should be considered as a possible cause of chest infection, particularly in patients with appropriately positive blood cultures and no other positive microbiological finding.