Non-communicable respiratory disease in Malawi: a systematic review and meta-analysis

BackgroundNon-communicable respiratory diseases are important contributors to morbidity and mortality in sub-Saharan African countries such as Malawi. AimTo conduct a systematic review of the available literature relating to chronic respiratory disease in Malawi. MethodsWe conducted a systematic protocol-driven literature search of key scientific databases including Scopus and Medline. Papers were independently assessed for eligibility by two authors and included if they reported objective measures (including self-reported standard symptoms) of chronic respiratory disease and were conducted in Malawi. A meta-analysis of available estimates was then conducted. We re-analysed data from three of these studies in a secondary data analysis to allow for between-study comparisons. ResultsOur search identified 393 papers of which 17 (5 involving children and 12 involving adults) met the inclusion criteria. Wheeze was the symptom most frequently reported in children in the community (12.1%), hospital (11.2%) and HIV clinic (8.1%) settings. Cough was the symptom most frequently reported by adults in the community (3–18%). Spirometric abnormalities varied substantially between studies. For example, in adults, airflow obstruction varied between 2.3% and 20% and low forced vital capacity (FVC) varied between 2.7% and 52.8%. ConclusionWe identified a high burden of chronic respiratory symptoms and abnormal spirometry (particularly low FVC) within paediatric and adult populations in Malawi. The estimates for country-wide burden related to this disease were limited by the heterogeneity of the methods used to assess symptoms and spirometry. There is an urgent need to develop a better understanding of the determinants and natural history of non-communicable respiratory disease across the life-course in Malawi

By focusing on outputs, rather than people, we misunderstand the real impact of research.

Arguing that science policy remains shaped by enduring ideas of linear knowledge transfer from research to society, Paul Nightingale and Rebecca Vine, propose that research impact in contemporary service economies lies predominantly within the application of human expertise to complex problems. By focusing on researchers, rather than research, they suggest research systems would be better positioned to appreciate the multifaceted ways in which fields of research, such as the social sciences, impact society

Exploring the natural history and determinants of chronic respiratory disease in high-risk populations: perspectives from the UK and Malawi

Chronic respiratory disease affects over 500 million worldwide, with 251 million people suffering from Chronic Obstructive Pulmonary Disease (COPD) causing approximately 3 million deaths a year. In the global North tobacco smoke is known to be a risk factor for COPD, but little is known about the risks of other inhaled substances, such as heroin or the natural history of any respiratory disease associated with it. In the global South there is limited literature describing the burden of chronic respiratory disease or its natural history, with a particular lack of research amongst the more disadvantaged, harder to reach populations in sub-Saharan Africa. These populations have known high risk exposure including biomass use and a high burden of HIV and Tuberculosis. The gap in evidence provides an opportunity to explore the natural history and determinates of three potentially high-risk groups, the first heroin smokers in Liverpool UK, the second users of biomass fuel in rural Malawi, and thirdly those who have completed treatment for tuberculosis (TB) in urban Malawi. The introduction chapter explains the rationale behind this thesis and highlights the key literature available in each population. The thesis then presents 5 papers, using different methods to explore chronic respiratory disease in these three populations. The data presented from Liverpool (Study 1: Screening heroin smokers attending community drug clinics for change in lung function: a cohort study) reports heroin users as being at significant risk of COPD. We found that forced expiratory volume in 1 second (FEV1) declined annually by 90ml (SD 190, p<0.001) which is significantly worse than you would expect in tobacco smokers. In the same population, study 2 (COPD in heroin smokers: a patient perspective) reports that accessing care and correct use of medication was a major problem that needs addressing. In a move from the global North to the global South, I report that the prevalence of chronic respiratory symptoms, spirometric obstruction and restriction in populations using biomass as their main fuel were 13·6% (95% CI:11.9-15.4), 8·7% (95% CI:7·0-10·7) and 34·8% (95% CI:31·7-38·0), respectively (Study 3: Noncommunicable respiratory disease and air pollution exposure in Malawi: a cross-sectional study). A systematic review and meta-analysis attempted to estimate the overall burden of chronic respiratory disease in Malawi but noted the heterogeneity of the available data. Airflow obstruction in adults varied between 2.3% and 20% and low FVC between 2.7% and 52.8%. (Study 4: Non-communicable respiratory disease in Malawi: a systematic review and meta-analysis). One possible cause of the high levels of abnormal spirometry and respiratory symptoms seen in Malawi could be Post-TB respiratory disease with study 5 (Respiratory symptoms and lung function in patients treated for pulmonary tuberculosis in Malawi: a prospective cohort study) highlighting that over a quarter of patients still have abnormal spirometry 3-years after TB-treatment completion. The proportions of participants with low FVC and obstruction changed from 57/285(20.0%) and 41/285(14.4%) at TB treatment completion to 34/272(12.5%) and 43/272(15.8%) at 3-years. All three populations presented in this thesis live with a significant burden of respiratory disease, often in disadvantaged situations where accessing optimal healthcare can be a challenge. Managing lung health in these populations requires careful planning with further research required into setting appropriate treatment options

Noncommunicable Respiratory Disease and Air Pollution Exposure in Malawi (CAPS). A Cross-Sectional Study.

RationaleNoncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults.ObjectivesWe set out to explore the prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi.MethodsWe performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS [Cooking and Pneumonia Study]) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter &lt;2.5 μm in aerodynamic diameter [PM2.5] and carbon monoxide [CO]). Weighted prevalence estimates were calculated; multivariable and intention-to-treat analyses were done.Measurements and main resultsOne thousand four hundred eighty-one participants (mean [SD] age, 43.8 [17.8] yr; 57% female) were recruited. The prevalence of chronic respiratory symptoms, spirometric obstruction, and restriction were 13.6% (95% confidence interval [CI], 11.9-15.4), 8.7% (95% CI, 7.0-10.7), and 34.8% (95% CI, 31.7-38.0), respectively. Median 48-hour personal PM2.5 and CO exposures were 71.0 μg/m3 (interquartile range [IQR], 44.6-119.2) and 1.23 ppm (IQR, 0.79-1.93), respectively. Chronic respiratory symptoms were associated with current/ex-smoking (odds ratio [OR], 1.59; 95% CI, 1.05-2.39), previous tuberculosis (OR, 2.50; 95% CI, 1.04-15.58), and CO exposure (OR, 1.46; 95% CI, 1.04-2.05). Exposure to PM2.5 was not associated with any demographic, clinical, or spirometric characteristics. There was no effect of the CAPS intervention on any of the secondary trial outcomes.ConclusionsThe burden of chronic respiratory symptoms, abnormal spirometry, and air pollution exposures in adults in rural Malawi is of considerable potential public health importance. We found little evidence that air pollution exposures were associated with chronic respiratory symptoms or spirometric abnormalities and no evidence that the CAPS intervention had effects on the secondary trial outcomes. More effective prevention and control strategies for noncommunicable respiratory disease in sub-Saharan Africa are needed. Clinical trial registered with www.isrctn.com (ISRCTN 59448623)

Non-Communicable Respiratory Disease and Air Pollution Exposure in Malawi (CAPS): A Cross-Sectional Study

Background Non-communicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults. Methods We did a cross-sectional study among adults in communities participating in a randomised controlled trial of a cleaner-burning biomass-fuelled cookstove intervention (CAPS) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, personal exposure to air pollution (fine particulate matter (PM2.5) and carbon monoxide (CO)). Weighted prevalence estimates were calculated; multivariable and intention-to-treat analyses were done. Results 1481 participants (mean (SD)) age 43·8 (17·8)) 57% female) were recruited. The prevalence of chronic respiratory symptoms, spirometric obstruction and restriction were 13·6% (95% CI:11.9-15.4), 8·7% (95% CI:7·0-10·7) and 34·8% (95% CI:31·7-38·0), respectively. Median 48-hour personal PM2.5 and CO exposures were 71·0 μg/m3 (IQR:44·6-119·2) and 1·23 ppm (IQR:0·79-1·93), respectively. Chronic respiratory symptoms were associated with current/ex-smoking (OR=1·59 (95% CI:1·05-2·39)), previous TB (OR=2·50 (95% CI:1·04-15·58)) and CO exposure (OR=1·46 (95% CI:1·04-2·05)). Exposure to PM2.5 was not associated with any demographic, clinical or spirometric characteristics. There was no effect of the CAPS intervention on any of the secondary trial outcomes. Conclusion The burden of chronic respiratory symptoms, abnormal spirometry and air pollution exposures in adults in rural Malawi is of considerable potential public health importance. We found little evidence that air pollution exposures were associated with chronic respiratory symptoms or spirometric abnormalities and no evidence that the CAPS intervention had effects on the secondary trial outcomes. More effective prevention and control strategies for non-communicable respiratory disease in sub-Saharan Africa are needed

Non-communicable respiratory disease in Malawi: a systematic review and meta-analysis

Background Non-communicable respiratory diseases are important contributors to morbidity and mortality in sub-Saharan African countries such as Malawi. Aim To conduct a systematic review of the available literature relating to chronic respiratory disease in Malawi. Methods We conducted a systematic protocol-driven literature search of key scientific databases including Scopus and Medline. Papers were independently assessed for eligibility by two authors and included if they reported objective measures (including self-reported standard symptoms) of chronic respiratory disease and were conducted in Malawi. A meta-analysis of available estimates was then conducted. We re-analysed data from three of these studies in a secondary data analysis to allow for between-study comparisons. Results Our search identified 393 papers of which 17 (5 involving children and 12 involving adults) met the inclusion criteria. Wheeze was the symptom most frequently reported in children in the community (12.1%), hospital (11.2%) and HIV clinic (8.1%) settings. Cough was the symptom most frequently reported by adults in the community (3–18%). Spirometric abnormalities varied substantially between studies. For example, in adults, airflow obstruction varied between 2.3% and 20% and low forced vital capacity (varied between 2.7% and 52.8%. Conclusion We identified a high burden of chronic respiratory symptoms and abnormal spirometry (particularly low FVC) within paediatric and adult populations in Malawi. The estimates for country-wide burden related to this disease were limited by the heterogeneity of the methods used to assess symptoms and spirometry. There is an urgent need to develop a better understanding of the determinants and natural history of non-communicable respiratory disease across the life-course in Malawi

Exploring perspectives on chronic obstructive pulmonary disease in people who smoke heroin: a qualitative study

Background Smoking rather than injecting heroin has become more common over the last twenty years. Although there is an increasing body of evidence describing high levels of COPD in heroin smokers, there is limited evidence documenting the impact this has on this population group. Aim. We aimed to describe the experiences of heroin smokers with COPD in Liverpool, UK Design and Setting Participants were purposefully sampled for this qualitative study. Participants included were adults enrolled in an opioid replacement clinic run by Addaction in Liverpool, UK and whom had already engaged with spirometry testing for COPD as part of a previous study Methods. We preformed semi-structured interviews with participants with spirometrically-confirmed COPD in opioid replacement clinics in Liverpool, UK. Data were analysed using a framework analysis approach. Results. We invited 16 potential participants of whom 10 agreed to take part and were interviewed. Three themes common to all interviews were identified: functional measures of lung health that impacted on their activities of daily living, inhaler and medication perceptions with erratic use that was not concordant with their prescription, and the impact of difficulties accessing care. Conclusion. These findings, along with previous studies highlighting the prevalence of COPD in this population, warrant efforts to integrate community COPD and opioid replacement services to improve outcomes for this vulnerable population

Clinical Methods and Design for a Phase II Randomised Control Trial to Assess the Efficacy and Safety of an 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) in Idiopathic Intracranial Hypertension: IIH:DT

Background: Idiopathic intracranial hypertension (IIH) is a condition with few effective management options. So far, there have been no randomized controlled trials evaluating new treatments in IIH.Objectives: The purpose of this paper is to outline the trial design for the Idiopathic Intracranial Hypertension Drug Trial (IIH:DT), assessing an innovative medical treatment in IIH and the rationale for the chosen trial methodology.Methods: IIH:DT is a phase II double-blind randomized placebo-controlled trial recruiting 30 female participants with active IIH (intracranial pressure >25cm H2 O and papilledema). Participants are randomized in a 1:1 ratio to 12 weeks of either AZD4017, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, or a matching placebo. They receive either 400 mg of AZD4017 or placebo twice daily. Participants are followed up at Weeks 1, 2, 3, 4, 6, 8, 10, 12, and 16 postrandomization. The primary outcome is to examine the effect of AZD4017 on intracranial pressure, measured by lumbar puncture, over 12 weeks. Secondary outcome measures include IIH symptoms, visual function, papilledema, headache measures, safety, and tolerability. Cerebrospinal fluid, serum, plasma, urine, and adipose tissue are also taken for exploratory outcomes.Results: All participants were recruited between April 2014 and August 2016.Conclusions: IIH:DT is the first phase II double-blind randomized placebo-controlled trial assessing the efficacy and safety of the novel pharmacological intervention, AZD4017, for the treatment of IIH.Trial Registration: Clinicaltrials.gov NCT02017444; https://clinicaltrials.gov/ct2/show/NCT02017444 (Archived by WebCite at http://www.webcitation.org/6tVHesN6s

Is continuous positive airway pressure (CPAP) a new standard of care for type 1 respiratory failure in COVID-19 patients? A retrospective observational study of a dedicated COVID-19 CPAP service

The aim of this case series is to describe and evaluate our experience of continuous positive airway pressure (CPAP) to treat type 1 respiratory failure in patients with COVID-19. CPAP was delivered in negative pressure rooms in the newly repurposed infectious disease unit. We report a cohort of 24 patients with type 1 respiratory failure and COVID-19 admitted to the Royal Liverpool Hospital between 1 April and 30 April 2020. Overall, our results were positive; we were able to safely administer CPAP outside the walls of a critical care or high dependency unit environment and over half of patients (58%) avoided mechanical ventilation and a total of 19 out of 24 (79%) have survived and been discharged from our care

Is continuous positive airway pressure therapy in COVID-19 associated with an increased rate of pulmonary barotrauma?

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has infected over 150 million people worldwide, with over 3 million deaths as of 6 May 2021 [1]. In the UK, approximately 15% of individuals affected by coronavirus disease 2019 (COVID-19) have required admission to hospital [2] and those with severe disease require advanced respiratory support including invasive mechanical ventilation (IMV) [3]. Due to the considerable scale of the pandemic, noninvasive continuous positive airway pressure (CPAP) has been utilised for COVID-19-related type I respiratory failure as a therapeutic strategy to improve patient outcomes [4, 5] and also to preserve IMV capacity during a challenging time for acute healthcare providers. However, its exact role is unclear and is the subject of a UK multicentre trial [6]