Availability, cost and affordability of essential medicines for chronic respiratory diseases in low-income and middle-income countries: a cross-sectional study.

Contemporary data on the availability, cost and affordability of essential medicines for chronic respiratory diseases (CRDs) across low-income and middle-income countries (LMICs) are missing, despite most people with CRDs living in LMICs. Cross-sectional data for seven CRD medicines in pharmacies, healthcare facilities and central medicine stores were collected from 60 LMICs in 2022-2023. Medicines for symptomatic relief were widely available and affordable, while preventative treatments varied widely in cost, were less available and largely unaffordable. There is an urgent need to address these issues if the Sustainable Development Goal 3 is to be achieved for people with asthma by 2030.

Lung Cancer Presents at a Younger Age and Is Less Likely to be Curable in People Living with HIV.

INTRODUCTION: Globally, lung cancer remains the leading cause of malignancy-related death in men and women. There is increasing evidence that the risk for lung cancer in people living with human immunodeficiency virus (PLHIV) is higher than that of the general population. Given the high burden of PLHIV and lung cancer in Southern Africa, we aimed to compare the characteristics of PLHIV and HIV-negative lung cancer patients with regards to demographics, cell type, performance status, and tumour stage at presentation. METHODS: All patients who presented to a large tertiary hospital over a 7-year period with a confirmed tissue diagnosis of primary lung cancer were included in a prospective registry. The patient demographics, HIV status, as well as the patients' performance status according to the Eastern Cooperative Oncology Group (ECOG) were documented. RESULTS: The cohort consisted of 1,805 patients (mean age 60.0 years) of which 1,129 were male. In total, 133 were PLHIV and 1,292 were confirmed HIV-negative, while the remaining were categorised as HIV-unknown. PLHIV with lung cancer were found to be younger than the HIV-negative group (mean [±SD] 54.6 [9.3] versus 60.3 [10.1], p < 0.001). Notably, not a single PLHIV was diagnosed with resectable non-small cell lung cancer (NSCLC), and only 7 of 133 (6.5%) had potentially curable disease NSCLC (up to stage IIIB) compared to 240 of 1292 HIV-negative patients (27.7%, p < 0.001). CONCLUSION: PLHIV with lung cancer were diagnosed at a significantly younger age and were significantly less likely to have curable NSCLC at presentation.

"Asthma is a very bully disease" - patient experiences of living with chronic respiratory diseases in Cape Town, South Africa.

BACKGROUND: Chronic respiratory diseases are common in Cape Town, South Africa. Yet the experiences of how adults with these conditions, such as asthma or COPD (chronic obstructive pulmonary disease), negotiate the health system are poorly understood. Qualitative methodology lends itself to investigate this question. AIM OF STUDY: To explore the "emic" experiences of adults with CRDs in Cape Town when they were negotiating the health system using semi-structured interviews. METHODS: Interviews were conducted following informed consent with purposively sampled adults who had attended public hospitals in Cape Town with chronic respiratory disease flare-ups. This work was nested in the quantitative "Diagnosing Airways Disease" study. The topic guide explored patients' experiences of accessing healthcare including receiving and interpretations of the diagnosis and management, and impacts on daily life. Interviews were conducted in Afrikaans, isiXhosa, or English; transcribed, and translated into English and thematically analysed until saturation. RESULTS: Thirty-two interviews (16 in Afrikaans, 8 in isiXhosa, 8 in English) were completed in 2022. 17 women and 15 men participated. Most participants were older than 50 years (25/32), and most were unemployed (13/32) or retired (11/32). The identified themes were: Perceived causes of illness; experiences of healthcare; perceived risks and barriers when accessing healthcare; and impact on earnings. The perceived causes of their illness and risks were structural, and included air pollution, poor quality housing, occupational exposures, limited healthcare services, and fear of violence. These factors led to self-treatment, sharing of medicines, and delay in receiving a diagnosis. Many paid privately for treatments or services to overcome identified shortcomings of the public healthcare system, and many reported additional significant indirect costs. Being ill had a profound impact on income. The identified themes were explored through the lens of "structural violence", where "social structures stop individuals … from reaching their full potential" (Galtung, 1969). CONCLUSION: In Cape Town structural elements such as stretched healthcare professionals, insufficiently enforced policies on e.g., housing or work-place exposures, poverty and crime made it difficult for participants to successfully navigate their illness experience. It forced some to pay out of pocket to receive perceived better healthcare privately.

UMOYA: a prospective longitudinal cohort study to evaluate novel diagnostic tools and to assess long-term impact on lung health in South African children with presumptive pulmonary TB-a study protocol.

BACKGROUND: Despite a high paediatric tuberculosis (TB) burden globally, sensitive and specific diagnostic tools are lacking. In addition, no data exist on the impact of pulmonary TB on long-term child lung health in low- and middle-income countries. The prospective observational UMOYA study aims (1) to build a state-of-the-art clinical, radiological, and biological repository of well-characterised children with presumptive pulmonary TB as a platform for future studies to explore new emerging diagnostic tools and biomarkers for early diagnosis and treatment response; and (2) to investigate the short and long-term impact of pulmonary TB on lung health and quality of life in children. METHODS: We will recruit up to 600 children (0-13 years) with presumptive pulmonary TB and 100 healthy controls. Recruitment started in November 2017 and is expected to continue until May 2023. Sputum and non-sputum-based samples are collected at enrolment and during follow-up in TB cases and symptomatic controls. TB treatment is started by routine care services. Intensive follow-up for 6 months will allow for TB cases to retrospectively be classified according to international consensus clinical case definitions for TB. Long-term follow-up, including imaging, comprehensive assessment of lung function and quality of life questionnaires, are done yearly up to 4 years after recruitment. DISCUSSION: The UMOYA study will provide a unique platform to evaluate new emerging diagnostic tools and biomarkers for early diagnosis and treatment response and to investigate long-term outcomes of pulmonary TB and other respiratory events on lung health in children.

Improving lung health in low-income and middle-income countries: from challenges to solutions.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

Clinical features and outcomes of COVID-19 admissions in a population with a high prevalence of HIV and tuberculosis: a multicentre cohort study.

BACKGROUND: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB). METHODS: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed. RESULTS: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels. CONCLUSION: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.

Autologous Blood Patch Pleurodesis for the Management of a Persistent Air Leak after Secondary Spontaneous Pneumothorax.

Patients with secondary spontaneous pneumothorax (SSP) complicated by persistent air leak (PAL) and who are poor surgical candidates have limited treatment options. This case series explored autologous blood patch pleurodesis as a possible cost-effective management option. A total of 46 episodes of SSP with PAL were included. The procedure was successful in 33 (71.7%). Of these, 17 (51.5%) resolved within 1 day. The mean duration of intercostal drainage prior to the blood patch was 22 days in the successful group. Pneumothoraces with incomplete lung re-expansion at the time of procedure were successful in 20 of 30 (66.7%). Only human immunodeficiency virus infection was associated with failure (p = 0.03). Adverse events included transient fever (n = 3) that resolved spontaneously, and empyema (n = 3) which were successfully managed with antibiotics and pigtail drainage. We conclude that a large proportion of patients with SSP complicated by PAL who are unfit for surgery may be liberated from intercostal drainage by an autologous blood patch pleurodesis, with minimal adverse effects.

Diagnosing Tuberculosis: What Do New Technologies Allow Us to (Not) Do?

New tuberculosis (TB) diagnostics are at a crossroads: their development, evaluation, and implementation is severely damaged by resource diversion due to COVID-19. Yet several technologies, especially those with potential for non-invasive non-sputum-based testing, hold promise for efficiently triaging and rapidly confirming TB near point-of-care. Such tests are, however, progressing through the pipeline slowly and will take years to reach patients and health workers. Compellingly, such tests will create new opportunities for difficult-to-diagnose populations, including primary care attendees (all-comers in high burden settings irrespective of reason for presentation) and community members (with early stage disease or risk factors like HIV), many of whom cannot easily produce sputum. Critically, all upcoming technologies have limitations that implementers and health workers need to be cognizant of to ensure optimal deployment without undermining confidence in a technology that still offers improvements over the status quo. In this state-of-the-art review, we critically appraise such technologies for active pulmonary TB diagnosis. We highlight strengths, limitations, outstanding research questions, and how current and future tests could be used in the presence of these limitations and uncertainties. Among triage tests, CRP (for which commercial near point-of-care devices exist) and computer-aided detection software with digital chest X-ray hold promise, together with late-stage blood-based assays that detect host and/or microbial biomarkers; however, aside from a handful of prototypes, the latter category has a shortage of promising late-stage alternatives. Furthermore, positive results from new triage tests may have utility in people without TB; however, their utility for informing diagnostic pathways for other diseases is under-researched (most sick people tested for TB do not have TB). For confirmatory tests, few true point-of-care options will be available soon; however, combining novel approaches like tongue swabs with established tests like Ultra have short-term promise but first require optimizations to specimen collection and processing procedures. Concerningly, no technologies yet have compelling evidence of meeting the World Health Organization optimal target product profile performance criteria, especially for important operational criteria crucial for field deployment. This is alarming as the target product profile criteria are themselves almost a decade old and require urgent revision, especially to cater for technologies made prominent by the COVID-19 diagnostic response (e.g., at-home testing and connectivity solutions). Throughout the review, we underscore the importance of how target populations and settings affect test performance and how the criteria by which these tests should be judged vary by use case, including in active case finding. Lastly, we advocate for health workers and researchers to themselves be vocal proponents of the uptake of both new tests and those - already available tests that remain suboptimally utilized.

Post-Tuberculosis Lung Disease: Clinical Review of an Under-Recognised Global Challenge.

An estimated 58 million people have survived tuberculosis since 2000, yet many of them will suffer from post-tuberculosis lung disease (PTLD). PTLD results from a complex interplay between organism, host, and environmental factors and affects long-term respiratory health. PTLD is an overlapping spectrum of disorders that affects large and small airways (bronchiectasis and obstructive lung disease), lung parenchyma, pulmonary vasculature, and pleura and may be complicated by co-infection and haemoptysis. People affected by PTLD have shortened life expectancy and increased risk of recurrent tuberculosis, but predictors of long-term outcomes are not known. No data are available on PTLD in children and on impact throughout the life course. Risk-factors for PTLD include multiple episodes of tuberculosis, drug-resistant tuberculosis, delays in diagnosis, and possibly smoking. Due to a lack of controlled trials in this population, no evidence-based recommendations for the investigation and management of PTLD are currently available. Empirical expert opinion advocates pulmonary rehabilitation, smoking cessation, and vaccinations (pneumococcal and influenza). Exacerbations in PTLD remain both poorly understood and under-recognised. Among people with PTLD, the probability of tuberculosis recurrence must be balanced against other causes of symptom worsening. Unnecessary courses of repeated empiric anti-tuberculosis chemotherapy should be avoided. PTLD is an important contributor to the global burden of chronic lung disease. Advocacy is needed to increase recognition for PTLD and its associated economic, social, and psychological consequences and to better understand how PTLD sequelae could be mitigated. Research is urgently needed to inform policy to guide clinical decision-making and preventative strategies for PTLD.

Relative Sparing of the Left Upper Zone on Chest Radiography in Severe COVID-19 Pneumonia.

The radiological findings of COVID-19 are well-described, including its evolution. In an earlier report of admission chest radiographs of patients with COVID-19, we anecdotally noted relative sparing of the left upper zone (LUZ). We subsequently aimed to describe the main chest radiograph findings in another cohort, focusing on zonal predominance. The admission chest radiographs of 111 patients with CO-VID-19 pneumonia requiring intensive care admission were reviewed by 2 thoracic radiologists and categorized according to the predominant pattern into either ground-glass opacities (GGOs), alveolar infiltrates and/or consolidation, or reticular and/or nodular infiltrates or an equal combination of both, and the extent of disease involvement of each of the zones using a modified Radiologic Assessment of Lung Edema (RALE) score. Parenchymal changes were detected in all. In total, 106 radiographs showed GGOs, alveolar infiltrates, and/or consolidation, and 5 had a combination of reticular/nodular infiltrates as well as GGOs, alveolar infiltrates, and/or consolidation. The LUZ had a significant lower grading score than the right upper zone: 1 versus 2 (p < 0.001). Likewise, the upper zones had a significant lower score than the mid and lower zones (p < 0.001). Our findings confirmed the relative sparing of the LUZ in severe COVID-19 pneumonia.

The effect of HIV-associated tuberculosis, tuberculosis-IRIS and prednisone on lung function.

Residual pulmonary impairment is common after treatment for tuberculosis (TB). Lung function data in patients with HIV-associated TB are scarce, especially in the context of paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) and prophylactic prednisone. We aimed to determine the prevalence of lung function abnormalities in patients with HIV-associated TB and CD4 counts ≤100 cells·µL-1 and assess the effect of prophylactic prednisone and the development of paradoxical TB-IRIS on pulmonary impairment.We performed spirometry, 6-min walk test (6MWT) and chest radiography at baseline (week 0) and at weeks 4, 12 and 28 in participants of the PredART trial, which evaluated a 28-day course of prednisone to prevent TB-IRIS in patients with HIV-associated TB commencing antiretroviral therapy.153 participants underwent spirometry and/or 6MWT at one or more time points. Abnormal spirometry measurements were present in 66% of participants at week 0 and 50% at week 28; low forced vital capacity was the commonest abnormality. Chest radiographs showed little or no abnormalities in the majority of participants. Prednisone use resulted in a 42 m greater 6-min walk distance and a 4.9% higher percentage of predicted forced expiratory volume in 1 s at week 4; these differences were no longer significantly different from week 12 onwards. TB-IRIS did not significantly impair lung function outcome.Residual pulmonary impairment is common in HIV-associated TB. In patients with low CD4 counts, neither prophylactic prednisone as used in our study nor the development of TB-IRIS significantly affected week-28 pulmonary outcome.

Pulmonary hypertension in majority countries: opportunities amidst challenges.

PURPOSE OF REVIEW: Pulmonary hypertension is a deadly disease, the causes of which vary between geographical regions. Eighty four percentage of the world's population lives in majority countries (also called low-income and middle-income countries), yet data on pulmonary hypertension in these settings are proportionally scarce. This article provides a review of pulmonary hypertension in majority countries, focusing in detail on the most common causes in these regions, and highlights contextual challenges faced. RECENT FINDINGS: Epidemiological data confirms a complex and overlapping array of causes, with pulmonary hypertension because of conditions such as rheumatic heart disease, HIV, schistosomiasis, chronic lung disease and sickle cell disease. Delayed pulmonary hypertension diagnosis remains a concern and is ascribed to a lack of resources and lack of pulmonary hypertension awareness by health professionals. Pulmonary hypertension diagnosis is frequently considered once signs of right heart failure emerge, while echocardiography and right heart catheterization are unavailable in many settings. Accurate data on the prevalence of pulmonary hypertension in many of these regions are needed and could be achieved by establishing and frequent review of national databases where the incident and prevalent pulmonary hypertension cases are captured. SUMMARY: There is urgent need for pulmonary hypertension advocacy among clinicians in the primary, secondary and tertiary healthcare sectors of majority countries, and validated noninvasive diagnostic algorithms are needed. Increased awareness and early diagnosis are likely to improve outcomes of pulmonary hypertension patients in these regions, and potentially stimulate locally relevant research.

COVID-19 in Africa: care and protection for frontline healthcare workers.

Medical staff caring for COVID-19 patients face mental stress, physical exhaustion, separation from families, stigma, and the pain of losing patients and colleagues. Many of them have acquired SARS-CoV-2 and some have died. In Africa, where the pandemic is escalating, there are major gaps in response capacity, especially in human resources and protective equipment. We examine these challenges and propose interventions to protect healthcare workers on the continent, drawing on articles identified on Medline (Pubmed) in a search on 24 March 2020. Global jostling means that supplies of personal protective equipment are limited in Africa. Even low-cost interventions such as facemasks for patients with a cough and water supplies for handwashing may be challenging, as is 'physical distancing' in overcrowded primary health care clinics. Without adequate protection, COVID-19 mortality may be high among healthcare workers and their family in Africa given limited critical care beds and difficulties in transporting ill healthcare workers from rural to urban care centres. Much can be done to protect healthcare workers, however. The continent has learnt invaluable lessons from Ebola and HIV control. HIV counselors and community healthcare workers are key resources, and could promote social distancing and related interventions, dispel myths, support healthcare workers, perform symptom screening and trace contacts. Staff motivation and retention may be enhanced through carefully managed risk 'allowances' or compensation. International support with personnel and protective equipment, especially from China, could turn the pandemic's trajectory in Africa around. Telemedicine holds promise as it rationalises human resources and reduces patient contact and thus infection risks. Importantly, healthcare workers, using their authoritative voice, can promote effective COVID-19 policies and prioritization of their safety. Prioritizing healthcare workers for SARS-CoV-2 testing, hospital beds and targeted research, as well as ensuring that public figures and the population acknowledge the commitment of healthcare workers may help to maintain morale. Clearly there are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic's potentially devastating heath, socio-economic and security impacts on the continent.

Endobronchial Valve Used as Salvage Therapy in a Mechanically Ventilated Patient with Intractable Life-Threatening Haemoptysis.

Treatment options for intractable life-threatening haemoptysis in mechanically ventilated patients with structural lung disease who do not respond to bronchial artery embolisation (BAE) and who are deemed unfit for surgery are limited. A 26-year-old HIV-positive male with a poorly preserved CD4 count and active pulmonary tuberculosis was intubated and mechanically ventilated for persistent life-threatening haemoptysis. Two attempts at BAE failed, and life-threatening haemoptysis recurred daily for 14 days despite antituberculous therapy. He was deemed unfit for surgery during that period. We proceeded to identify the source of bleeding endoscopically and implanted an endobronchial valve in the left upper lobe bronchus. Following the collapse of the affected lobe, haemoptysis ceased and the patient was promptly liberated from mechanical ventilation. He remained haemoptysis free for the duration of his hospitalisation. Endobronchial valves, therefore, may be a viable option in patients mechanically ventilated with persistent life-threatening haemoptysis in whom all other conventional measures fail and who are considered unfit for surgery.

Can Large Hydatid Cysts Resolve with Medical Treatment Alone?

A 66-year-old female from a rural area in South Africa presented with non-life-threatening haemoptysis. Radiologic and serological investigations attributed her symptoms to bilateral, large echinococcal cysts. She declined surgery despite her lung physiologic parameters, which deemed her eligible. Medical therapy with oral albendazole was initiated with excellent clinical and radiologic response during a follow-up period of 18 months. To our knowledge, this is one of the first reported cases in the literature that shows complete resolution of bilateral large echinococcal cysts with medical treatment alone in an adult patient.

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 U.S.A. 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.