Asthma in the intensive care unit: A review of patient characteristics and outcomes.

Background: Most asthma-related deaths occur in low- and middle-income countries, and South Africa (SA) is ranked fifth in global asthma mortality. Little is known about the characteristics and outcome of asthma patients requiring intensive care unit (ICU) admission in SA. Objectives: To identify and characterise patients with acute severe asthma admitted to the respiratory ICU at Groote Schuur Hospital, Cape Town, SA, in order to evaluate outcomes and identify predictors of poor outcomes in those admitted. Methods: We performed a retrospective descriptive study of patients with severe asthma admitted to the respiratory ICU at Groote Schuur Hospital between 1 January 2014 and 31 December 2019. Results: One hundred and three patients (110 admission episodes) were identified with an acute asthma exacerbation requiring ICU admission; all were mechanically ventilated. There was a female preponderance (53.6%; n=59/110), with a median (range) age overall of 33 (13 - 84) years. Of all admissions, 40 (36.4%) were current tobacco smokers and 16 (14.5%) patients with a history of substance abuse. Two thirds (60.0%; n=66/110) of the patients were using an inhaled corticosteroid (ICS). No predictors of mortality were evident in multivariate modelling, although those who died were older, and had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores and longer duration of admission. Only 59 of the surviving 96 individual patients (61.5%) attended a specialist pulmonology clinic after discharge. Conclusion: Among patients admitted to the respiratory ICU at Groote Schuur Hospital for asthma exacerbations, there was a high prevalence of smokers and poor coverage with inhaled ICSs. Although mortality was low compared with general ICU mortality, more needs to be done to prevent acute severe asthma exacerbations. Study synopsis: What the study adds. Intensive care unit (ICU) admission represents the most severe form of exacerbation of asthma. South Africa (SA) has a very high rate of asthma deaths, and this study demonstrates that admission to an ICU with a very severe asthma exacerbation frequently results in a good outcome. However, many of the patients admitted to the ICU were not adequately treated with background asthma medications prior to their admission. Implications of the findings. Death from asthma should be avoidable, and admission to an ICU is not associated with high mortality. Patients are therefore likely to be dying at home or out of hospital. Better education and access to medication and early access to health services rather than improved in-hospital care would potentially alter SA's high asthma mortality.

Position statement on endoscopic lung volume reduction in South Africa: 2022 update.

Chronic obstructive pulmonary disease (COPD) remains one of the most common causes of morbidity and mortality in South Africa. Endoscopic lung volume reduction (ELVR) was first proposed by the South African Thoracic Society (SATS) for the treatment of advanced emphysema in 2015. Since the original statement was published, there has been a growing body of evidence that a certain well-defined sub-group of patients with advanced emphysema may benefit from ELVR, to the point where the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines and the United Kingdom National Institute for Health and Care Excellence (NICE) advocate the use of endoscopic valves based on level A evidence. Patients aged 40 - 75 years with severe dyspnoea (COPD Assessment Test score ≥10) despite maximal medical therapy and pulmonary rehabilitation, with forced expiratory volume in one second (FEV1) 20 - 50%, hyperinflation with residual volume (RV) >175% or RV/total lung capacity (TLC) >55% and a six-minute walking distance (6MWD) of 100 - 450 m (post-rehabilitation) should be referred for evaluation for ELVR, provided no contraindications (e.g. severe pulmonary hypertension) are present. Further evaluation should focus on the extent of parenchymal tissue destruction on high-resolution computed tomography (HRCT) of the lungs and interlobar collateral ventilation (CV) to identify a potential target lobe. Commercially available radiology software packages and/or an endobronchial catheter system can aid in this assessment. The aim of this statement is to provide the South African medical practitioner and healthcare funders with an overview of the practical aspects and current evidence for the judicious use of the valves and other ELVR modalities which may become available in the country.

Outcomes of patients with COVID-19 acute respiratory distress syndrome requiring invasive mechanical ventilation admitted to an intensive care unit in South Africa.

BACKGROUND: Up to 32% of patients with COVID-19 pneumonia may require intensive care unit (ICU) admission or mechanical ventilation. Data from low- and middle-income countries on COVID-19 acute respiratory distress syndrome (ARDS) are limited. Groote Schuur Hospital in Cape Town, South Africa, expanded its intensive care service to support patients with COVID-19 ARDS requiring invasive mechanical ventilation (IMV). OBJECTIVES: To report on patients' characteristics and outcomes from the first two pandemic waves. METHODS: All patients with COVID-19 ARDS admitted to the ICU for IMV were included in this prospective cohort study. Data were collected from 5 April 2020 to 5 April 2021. RESULTS: Over the 12-month study period, 461 patients were admitted to the designated COVID-19 ICU. Of these, 380 met the study criteria and 377 had confirmed hospital discharge outcomes. The median (range) age of patients was 51 (17 - 71) years, 50.5% were female, and the median (interquartile range (IQR)) body mass index was 32 (28 - 38) kg/m2. The median (IQR) arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio was 97 (71 - 128) after IMV was initiated. Comorbidities included diabetes (47.6%), hypertension (46.3%) and HIV infection (10.5%). Of the patients admitted, 30.8% survived to hospital discharge with a median (IQR) ICU length of stay of 19.5 (9 - 36) days. Predictors of mortality after adjusting for confounders were male sex (odds ratio (OR) 1.74), increasing age (OR 1.04) and higher Sequential Organ Failure Assessment (SOFA) score (OR 1.29). CONCLUSIONS: In a resource-limited environment, the provision of IMV support in the ICU achieved 30.8% hospital survival in patients with COVID-19 ARDS. The ability to predict survival remains difficult given this complex disease.

Position statement for adult and paediatric spirometry in South Africa: 2022 update.

Spirometry is required as part of the comprehensive evaluation of both adult and paediatric individuals with suspected or confirmed respiratory diseases and occupational assessments. It is used in the categorisation of impairment, grading of severity, assessment of potential progression and response to interventions. Guidelines for spirometry in South Africa are required to improve the quality, standardisation and usefulness in local respiratory practice. The broad principles of spirometry have remained largely unchanged from previous versions of the South African Spirometry Guidelines; however, minor adjustments have been incorporated from more comprehensive international guidelines, including adoption of the Global Lung Function Initiative 2012 (GLI 2012) spirometry reference equations for the South African population. All equipment should have proof of validation regarding resolution and consistency of the system. Daily calibration must be performed, and equipment quality control processes adhered to. It is important to have standard operating procedures to ensure consistency and quality and, additionally, strict infection control as highlighted during the COVID-19 pandemic. Adequate spirometry relies on a competent, trained operator, accurate equipment, standardised operating procedures, quality control and patient co-operation. All manoeuvres must be performed strictly according to guidelines, and strict quality assurance methods should be in place, including acceptability criteria (for any given effort) and repeatability (between efforts). Results must be categorised and graded according to current guidelines, taking into consideration the indication for the test.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience.

Background: There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting. Objectives: To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa. Methods: Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results: We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusion: Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis. Contributions of the study: We describe the organisational requirements to successfully expand critical care facilities and strategies to reduce the need for invasive mechanical ventilation in COVID-19 pneumonia. We also present the intensive care outcomes of these patients in a resource-constrained environment.

Guidelines for the management of asthma in adults and adolescents: Position statement of the South African Thoracic Society - 2021 update.

Asthma prevalence is increasing worldwide, and surveys indicate that most patients in developed and developing countries, including South Africa, do not receive optimal care and are therefore not well controlled. Standard management guidelines adapted to in-country realities are important to support optimal care. The South African Thoracic Society (SATS) first published a guideline for the management of chronic persistent asthma in 1992, which has subsequently been revised several times. The main aim of the present document was to revise and update SATS' statement on the suggested management of chronic asthma, based on the need to promote optimal care and control of asthma, together with the incorporation of new concepts and drug developments. This revised document reinforces optimal care and incorporates the following primary objectives to achieve the recent advances in asthma care: continued emphasis on the use of inhaled corticosteroids (ICS) as the foundation of asthma treatmentto reduce the reliance on short-acting beta-2 agonist (SABA) monotherapy for asthma symptomsto incorporate the evidence and strategy for the use of the combination of an ICS and formoterol for acute symptom relief (instead of a SABA)to incorporate the evidence and strategy for the use of as-needed ICS-long-acting beta agonists (LABA) for patients with infrequent symptoms or 'mild' asthmato incorporate the evidence and strategy for the use of a long-acting muscarinic antagonist (LAMA) in combination with ICS-LABA; andto incorporate the evidence and strategy for the use of and management with a biologic therapy in severe asthma.

Challenges for dedicated smoking cessation services in developing countries.

BACKGROUND: South Africa, ranked as the world's second most stressful country to live in, has an estimated 7 million smokers. A dedicated smoking cessation clinic established at Groote Schuur Hospital, Cape Town, provides the only clinical service and training centre in the country. OBJECTIVES: To evaluate the smokers attending the clinic, in order to better understand the requirements of smoking cessation services in resource-limited settings. METHODS: Demographic and smoking-related data were collected prospectively from all clinic attendees since its inception. Nicotine dependence, depression scores and exhaled carbon monoxide levels were formally evaluated. Consent was provided to review the data collected. RESULTS: Ninety-seven smokers were evaluated. Their mean (standard deviation) age was 50.9 (10.7) years, and 59% (57/97) were male. The median age of smoking initiation was 16 years (interquartile range (IQR) 8 - 28), with a current median daily consumption of 12 cigarettes (IQR 7 - 20). Overall, men smoked more than women, with a median of 20 cigarettes per day (IQR 10 - 20) v. 12 (IQR 5 - 20), respectively (p=0.001). The median Fagerström nicotine dependence score was 5 (IQR 3 - 7), with scores of 6 (IQR 4 - 8) for men and 5 (2 - 7) for women (p=0.06); 50% of smokers had a Fagerström score <6 (low to above-average dependence) and 22% a score ≥8 (extreme dependence). The median Patient Health Questionnnaire-9 (PHQ-9) depression score was 8 (IQR 4 - 11), and 49% of smokers had symptoms of at least minor depression (score ≥10). The clinic could not provide pharmacotherapy. The self-reported quit rate was 28% at median follow-up of 22 months (IQR 14 - 39). CONCLUSIONS: In smokers attempting to quit, moderate levels of nicotine dependence coexist with significant depression and anxiety symptoms. These data inform resource allocation and public health strategies, suggesting that in resource-limited smoking cessation services, psychological/behavioural support focusing on depressive symptoms may be a greater priority than simple pharmacotherapy.

Smoking cessation on the African continent: Challenges and opportunities.

Tobacco smoking is one of the world's single biggest preventable causes of death. Over 8 million people die each year of a tobacco-related illness - both directly and as a result of second-hand smoke. Combating this epidemic requires commitment from policy makers, healthcare workers and civil society. The WHO has invested extensively in supporting policy frameworks to assist countries to combat tobacco advertising, sales and promotion. Despite these interventions, over 1 billion people actively smoke, of whom >80% live in low- or middle-income countries. Strong policies, high taxation and cigarette pricing dissuade smokers effectively, but the clinician is frequently the individual who is faced with the smoker wishing to quit. Although many African countries have policies regarding tobacco control, very few have programmes to support smokers who wish to quit, and even fewer have active training programmes to equip healthcare practitioners to assist active smokers in breaking their addiction to nicotine. We present a perspective from several countries across the African continent, highlighting the challenges and opportunities to work together to build capacity for smoking cessation services throughout Africa.

Chronic obstructive pulmonary disease--diagnosis and classification of severity.

Chronic obstructive pulmonary disease (COPD) is a common, progressive and preventable non-communicable respiratory disorder. It is often confused with asthma and poorly understood by many lay people. The primary cause of COPD is tobacco smoking, but in the South African (SA) context, biomass fuel exposure/household pollution, tuberculosis, HIV and mining exposure are additional important causes.There is a very high prevalence of COPD in SA and it is the third leading cause of mortality globally.The diagnosis of COPD is based predominantly on symptoms, i.e. progressive shortness of breath and cough in a patient with risk factors­usually smoking. Lung function testing is required to formally make the diagnosis, which places a significant hurdle in correctly identifying COPD in SA, given the limited access to spirometry in many areas. Spirometry is also required to grade the severity of lung function obstruction.Severity assessment, which is used to plan a management strategy (predominantly bronchodilators with inhaled steroids in severe cases), combines symptoms, lung function and exacerbations. Based on these 3 factors, a patient can be categorised into 1 of 4 groups and appropriate management instituted. Additional comorbidities, particularly cardiovascular and mental illness, should also be evaluated.Early identification of COPD, with further avoidance of an aetiological cause such as smoking, is key in preventing disease progression.Appropriate therapy, comprising non-pharmacological and pharmacological interventions and based on a comprehensive severity assessment, should result in symptom improvement and reduced risk for exacerbations.

Assessment of previous tuberculosis status using questionnaires, chest X-rays and computed tomography scans.

SETTING: Accurate diagnosis of previous pulmonary tuberculosis disease (PPTB) status is important clinically and in research. Reliable records of bacteriologically confirmed tuberculosis (TB) are frequently unavailable. OBJECTIVES: To evaluate the use of questionnaires and chest imaging to determine PPTB status in a high TB prevalence population. DESIGN: PPTB status was assessed using two questionnaires, chest X-ray (CXR) and high-resolution chest computed tomography (CT) scans reported by experienced readers. The study population comprised adults aged >40 years diagnosed with obstructive lung disease in a community-based prevalence survey. RESULTS: The Burden of Obstructive Lung Disease (BOLD) questionnaire and a second comprehensive questionnaire (PTbQ) provided a history of PPTB in respectively 38% (n = 41) and 36.4% (n = 39) of 107 participants. On CXR, 43.3% (45/104) had evidence of PPTB, with good inter-reader agreement (κ = 0.73). Changes compatible with PPTB were identified on chest CT in 68.3% (71/104) of the subjects. Questionnaire and CXR had negative predictive values for PPTB of 48% and 47%, respectively, compared to a composite definition. CONCLUSION: Both questionnaire and CXR markedly underestimate the prevalence of previous TB in patients with chronic obstructive pulmonary disease. The combination of a structured questionnaire and CT scan is more useful when a diagnosis of PPTB needs to be ruled out.

Comparison of same day versus delayed enumeration of TB-specific T cell responses.

BACKGROUND/OBJECTIVE: Flexibility in sample processing may improve test utility of the quantitative antigen-specific T cell assay (T-SPOT.TB). We investigated whether delayed sample processing with and without the use of T-Cell Xtend, a proprietary reagent, impacted upon test accuracy. METHODS: Blood samples obtained from 363 sequentially recruited tuberculosis suspects or treated patients were processed immediately (day 0) and at different times after receipt of the sample [approximately 24-h (day 1) or approximately 32-h (day 2)] with and without adding T-Cell Xtend. RESULTS: T-Cell-Xtend-independent median ELISPOT counts (spot forming cells per million peripheral blood mononuclear cells) were significantly higher at day 1 versus day 0 (114 vs. 100; n=66; p=0.03); inter-time-point agreement between the results was 95.45% and the conversion/reversion rate was 4.55%. By contrast, counts on day 0 without T-Cell Xtend versus day 1 with T-Cell Xtend were similar (56 vs. 56; n=215), inter-time-point agreement between the results was 97.17%, and the conversion/reversion rate was 2.83%. Counts performed at day 2 with T-Cell Xtend were not significantly different from day 0. These findings were independent of HIV status. CONCLUSION: There was high agreement between results when samples were processed immediately and after a 24-h delay. However, although the use of T-Cell Xtend appeared to reduce the number of conversions/reversions this reduction was not statistically significant. Larger studies are required to clarify these findings.

Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD.

Tuberculosis (TB), smoking, HIV and chronic obstructive pulmonary disease (COPD) are burgeoning epidemics in developing countries. The link between TB and HIV is well established. Less well recognised is the strong relationship between tobacco smoking and the development and natural history of TB. These associations are of considerable relevance to public health and disease outcomes in individuals with TB. Moreover, tobacco smoking, a modifiable risk factor, is associated with poorer outcomes in HIV-associated opportunistic infections, of which TB is the commonest in developing countries. It is now also becoming clear that TB, like tobacco smoke, besides its known consequences of bronchiectasis and other pulmonary morbidity, is also a significant risk factor for the development of COPD. Thus, there is a deleterious and synergistic interaction between TB, HIV, tobacco smoking and COPD in a large proportion of the world's population. Further work, specifically mechanistic and epidemiological studies, is required to clarify the role of tobacco smoke on the progression of TB and HIV infection, and to assess the impact of smoking cessation interventions. These interactions deserve urgent attention and have major implications for coordinated public health planning and policy recommendations in the developing world.

Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.

BACKGROUND: The diagnosis of smear-negative pulmonary tuberculosis (TB) is problematic. There are limited data on the profile of alveolar TB antigen-specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB is unclear. METHODS: Antigen-specific interferon gamma (IFNgamma) responses to the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube), heparin-binding haemagglutinin and purified protein derivative were evaluated, using alveolar lavage cells, in 91 consecutively recruited South African patients suspected of having TB. RESULTS: Of 85 evaluable patients (29% HIV+), 24, 11, 48 and 2 had definite TB, probable TB, non-TB and an uncertain diagnosis, respectively. Between 34% (T-SPOT.TB) and 41% (QuantiFERON-TB-Gold-In-Tube) of all test results were inconclusive. Failure of the positive control was significantly higher with the QuantiFERON-TB-Gold-In-Tube than with T-SPOT.TB (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin B, compared with phytohaemagglutinin, substantially reduced failure of the positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite and non-TB groups were used for outcome analysis, the percentage sensitivity, specificity, positive predictive value and negative predictive value for T-SPOT.TB (> or = 20 spots/million alveolar mononuclear cells) and QuantiFERON-TB-Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69% (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.TB than with smear microscopy (14/24 (58%) vs. 7/24 (29%) of definite TB cases; p = 0.02). Heparin-binding haemagluttinin and purified protein derivative alveolar lymphocyte IFNgamma responses had poor performance outcomes. CONCLUSION: Provided evaluable results are obtained, the RD-1, but not the heparin-binding haemagglutinin or purified protein derivative, alveolar lymphocyte IFNgamma ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results.

Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis.

The clinical utility of antigen-specific interferon (IFN)-gamma release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification. We compared the diagnostic utility of unstimulated pleural IFN-gamma levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.(R)TB, QuantiFERON(R)-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard. Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.(R)TB: 86, 60, 84 and 64%, respectively; QuantiFERON(R)-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-gamma: 97, 100, 100 and 94%, respectively. Unstimulated IFN-gamma was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.