Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) has significantly contributed to global mortality, with three million deaths reported annually. This impact is expected to increase over the next 40 years, with approximately 5 million people predicted to succumb to COPD-related deaths annually. Immune mechanisms driving disease progression have not been fully elucidated. Airway microbiota have been implicated. However, it is still unclear how changes in the airway microbiome drive persistent immune activation and consequent lung damage. Mechanisms mediating microbiome-immune crosstalk in the airways remain unclear. In this review, we examine how dysbiosis mediates airway inflammation in COPD. We give a detailed account of how airway commensal bacteria interact with the mucosal innate and adaptive immune system to regulate immune responses in healthy or diseased airways. Immune-phenotyping airway microbiota could advance COPD immunotherapeutics and identify key open questions that future research must address to further such translation

Trends and level of control of hypertension among adults attending an ambulatory HIV clinic in Kampala, Uganda: a retrospective study.

BACKGROUND: With an ageing HIV-positive population, sub-Saharan Africa is now facing a dual epidemic of communicable and non-communicable diseases (NCDs). This study aimed to assess trends in the prevalence of hypertension and factors associated with hypertension, among adults attending an ambulatory HIV clinic in Kampala, Uganda. METHODS: We conducted a retrospective chart review to identify patients with hypertension. We used a random number generator to select 400 patient charts from each year from 2009 to 2014. Blood pressure, age, body mass index (BMI), WHO disease stage and Karnofsky scores were extracted. Logistic regression was used to estimate the strength of the association between each of these factors and the presence of hypertension. RESULTS: In total, 1996 charts were included in this analysis. The mean age of participants was 31 years and 1311/1996 (65.7%) were female. The overall prevalence of hypertension was 418/1996 (20.9%). This rose from 16.9% in 2009 to 32.3% in 2013. Of the patients with hypertension, 96/418 (23.0%) were receiving adequate treatment. Patients >50 years of age had 3.12 times the odds of hypertension compared with patients aged 20-29 years (95% CI 2.00 to 4.85). Men had 1.65 times the odds of hypertension compared with women (95% CI 1.34 to 2.03) and patients with a BMI of 35-39 kg/m2 had 3.93 times the odds of hypertension compared with patients with a BMI <25 kg/m2. CONCLUSIONS: The prevalence of hypertension is rising in the Ugandan HIV-positive population. There remains inadequate management and control of hypertension in this group highlighting the need to better integrate NCD care within the HIV clinical settings

Brief Report: Identification of Elite and Viremic Controllers From a Large Urban HIV Ambulatory Center in Kampala, Uganda.

BACKGROUND: Throughout the world, there are antiretroviral therapy-naive HIV+ individuals who maintain elevated peripheral CD4 T-cell counts, historically referred to as long-term nonprogressors (LTNPs). With recent improvements in viral load (VL) detection methods to levels as low as 20 copies per milliliter, 2 subsets of LTNPs have been defined: elite controllers (ECs), with undetectable VLs for at least 6-12 months, and viremic controllers (VCs), with VLs between 200 and 2000 copies per milliliter. ECs and VCs have been extensively studied in the developed world to determine underlying mechanisms responsible for virologic control. In sub-Saharan Africa, most studies have characterized LTNPs based on immunologic criteria making it difficult to compare findings with the Western cohorts, which use virologic criteria. Here, we describe a cohort of Uganda ECs and VCs attending a large HIV ambulatory center in Kampala, Uganda, based initially on CD4 counts and confirmed by repeated VL measurements. METHODS: A cross-sectional study was conducted among 14,492 HIV-infected, antiretroviral therapy-naive individuals aged 18 years and older under care for at least 5 years with serial peripheral CD4 counts ≥500 cells/μL. Among those, we determined the frequency of individuals with VLs <2000 copies per milliliter for at least 6 months. RESULTS: We report a prevalence of 0.26% (38/14,492) of HIV controllers in the clinic. We identified 36 ECs and 2 VCs. These individuals were middle-aged with an average CD4 count of 858 ± 172 (mean ± SD, 95% confidence interval: 795 to 921). Their average duration in HIV care was 7.4 ± 2.1 years (mean ± SD, 95% confidence interval: 6.6 to 8.1). The majority of EC/VCs were women (87%, 33/38), reflecting the demographics of the urban clinic. CONCLUSIONS: For the first time, this study demonstrates the frequency of EC/VCs in a large urban clinic in Uganda. Further study of these East African subjects may provide insights into how some individuals are able to control HIV in the absence of medications

Knowledge and use of family planning among men in rural Uganda.

BACKGROUND: Unmet need for family planning exceeds 33% in Uganda. One approach to decreasing unmet need is promoting male involvement in family planning. Male disapproval of use of family planning by their female partners and misconceptions about side effects are barriers to family planning globally and in Uganda in particular. Researchers have conducted a number of qualitative studies in recent years to examine different aspects of family planning among Ugandan men. The present study aimed to quantify men's knowledge of family planning in rural Uganda to understand how better to involve men in couples' contraceptive decision-making, particularly in low-resource settings. METHODS: Data were derived from in-person, researcher-administered surveys of men in a rural agrarian district in Uganda (N = 178). Participant demographics and knowledge of family planning methods, side effects, and use were queried. Descriptive statistics were used for analysis. RESULTS: Men were 34 years of age on average (range 18-71) and about half (56%) had a primary school education or less. Ninety-eight percent reported any knowledge of family planning, with 73% of men reporting obtaining information via radio and only 43% from health workers. The most common method known by men was the male condom (72%), but more than half also knew of injections (54%) and pills (52%). Relatively few men reported knowing about the most effective reversible contraceptive methods, intrauterine devices and implants (both 16%). Men identified many common contraceptive side-effects, such as vaginal bleeding (31%), and misconceptions about side effects, such as increased risk of infertility and birth defects, were relatively uncommon (both < 10%). About half of all men reported ever using a family planning method (53%), and 40% reported current use. CONCLUSIONS: This study's quantitative results build on those of recent qualitative studies and provide information about the types of family planning information men are lacking and avenues for getting this information to them

Association between Blood Pressure and HIV Status in Rural Uganda: Results of Cross-Sectional Analysis.

Introduction: The association between HIV status and hypertension is not well described within sub-Saharan Africa. We examined prevalence and risk factors for hypertension among HIV positive and negative individuals living in a rural district of Uganda. Methods: We conducted a cross-sectional analysis in two concurrent cohorts of 600 HIV negative and 721 HIV seropositive individuals aged ≥35 years. Results: Of the 721 HIV positive participants, 59.8% were women and the median age was 44.3 years, while for HIV negative individuals, 55% were women and the median age was 47.8 years. Over 90% of HIV positive individuals were on antiretroviral treatment. The prevalence of hypertension (≥140/≥90 mmHg) was 33.5% in HIV negative individuals and 23.9% in HIV positive individuals. Age (adjusted OR = 1.05, 95% CI 1.03 to 1.06) and BMI (adjusted OR = 1.08, 95% CI 1.05 to 1.12) were associated with higher odds of hypertension. Having HIV was associated with lower odds of hypertension (adjusted OR = 0.66, 95% CI 0.50 to 0.88), lower systolic blood pressure (-5.1 mmHg, 95% CI: -7.4 to -2.4) and lower diastolic blood pressure (-4.0 mmHg, 95% CI: -5.6 to -2.5). We did not observe differences in the odds of hypertension by CD4 count, viral load or ART among HIV positive individuals in this sample. Conclusions: Hypertension was prevalent in one third of HIV negative individuals and in one fourth of HIV positive patients. While access to health information among individuals attending HIV clinics may explain observed differences, more research is needed to understand plausible biological and social mechanisms that could explain lower blood pressure among people living with HIV in Uganda

Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Rationale: Detailed data on the characteristics and outcomes of patients with COVID-19 in sub-Saharan Africa are limited. Objective: We determined the clinical characteristics and treatment outcomes of patients diagnosed with COVID-19 in Uganda . Measurements: As of the 16 May 2020, a total of 203 cases had been confirmed. We report on the first 56 patients; 29 received hydroxychloroquine (HCQ) and 27 did not. Endpoints included admission to intensive care, mechanical ventilation or death during hospitalisation. Main results: The median age was 34.2 years; 67.9% were male; and 14.6% were 130/90 mm Hg, and 27.8% had BP of >140/90 mm Hg. Laboratory derangements were leucopenia (10.6%), lymphopenia (11.1%) and thrombocytopenia (26.3%). Abnormal chest X-ray was observed in 14.3%. No patients reached the primary endpoint. Time to clinical recovery was shorter among patients who received HCQ, but this difference did not reach statistical significance. Conclusion: Most of the patients with COVID-19 presented with mild disease and exhibited a clinical trajectory not similar to other countries. Outcomes did not differ by HCQ treatment status in line with other concluded studies on the benefit of using HCQ in the treatment of COVID-19.Publisher PDFPeer reviewe

1661. The association of spirometric impairment and history of TB: a population based study in Uganda

Abstract Background Pulmonary tuberculosis (TB) is the leading infectious cause of death globally with an estimated 1.7 billion people currently infected with Mycobacterium tuberculosis and at risk of developing TB. While the treatment of drug-susceptible pulmonary TB is highly effective, up to 50% of TB survivors have varying degrees of residual pathological and functional conditions potentially leading to chronic sequelae. Post-TB patients have reported respiratory symptoms, reduced quality of life, and increased risk of mortality. The objectives of this study are to describe the prevalence and lung function in individuals with post-TB exposure status in Uganda. Methods We performed a secondary data analysis of the Lung Function in Nakaseke and Kampala (LiNK) study, which is a population-based cohort in urban and rural settings in Uganda. Trained fieldworkers randomly selected homes and administered standard questionnaires to adults 35 years or older that were full-time residents of each setting. Prior TB diagnosis and treatment was self-reported by participants. Results Among the study population (N = 1559), 50 participants (3.2%) self-reported successfully treated TB. Among this subset of participants 21 (42.0%) were HIV positive, 9 (18.0%) were ever smokers, 6 (12.0%) were current smokers, and no participants had a prior COPD diagnosis. Mean (SD) age and body-mass index (BMI) at enrollment was 48.5 (SD 10.7) years and 22.2 (SD 3.9) kg/m2 respectively. The mean ± SD pre-bronchodilator FEV1/FVC was 72.9% (12.1%) for patients with successfully treated TB and 79.6% (0.08%) (p< 0.0001) for those without prior TB. Within these groups, 30% of patients with successfully treated TB and 9% of patients without prior TB had an FEV1/FVC suggestive of possible COPD. Comparison of FEV1/FVC Conclusion We found a high burden of residual effects of pulmonary TB on lung function and development of COPD, potentially increasing the global burden of COPD. Screening for chronic respiratory diseases following successful TB treatment is needed to improve lung function. Further research is needed to study lung function and quality of life in TB survivors in LMICs, where the burden of pulmonary TB is highest. Disclosures All Authors: No reported disclosure

The role of epigenetics in respiratory health in urban populations in low and middle-income countries

As urbanization increases in low- and middle-income countries (LMICs), urban populations will be increasingly exposed to a range of environmental risk factors for non-communicable diseases. Inadequate living conditions in urban settings may influence mechanisms that regulate gene expression, leading to the development of non-communicable respiratory diseases. We conducted a systematic review of the literature to assess the relationship between respiratory health and epigenetic factors to urban environmental exposures observed in LMICs using MEDLINE, PubMed, EMBASE, and Google Scholar searching a combination of the terms: epigenetics, chronic respiratory diseases (CRDs), lung development, chronic obstructive airway disease, and asthma. A total of 2835 articles were obtained, and 48 articles were included in this review. We found that environmental factors during early development are related to epigenetic effects that may be associated with a higher risk of CRDs. Epigenetic dysregulation of gene expression of the histone deacetylase (HDAC) and histone acetyltransferase gene families was likely involved in lung health of slum dwellers. Respiratory-related environmental exposures influence HDAC function and deoxyribonucleic acid methylation and are important risk factors in the development of CRD. Additional epigenetic research is needed to improve our understanding of associations between environmental exposures and non-communicable respiratory diseases

Chronic Obstructive Pulmonary Disease Prevalence and Associated Factors in a Setting of Well-Controlled HIV, A Cross-Sectional Study

In Sub-Saharan Africa, COPD remains prevalent but its association with HIV is not well characterized especially in rural settings. We assessed for COPD prevalence, associated factors and lung function profile among HIV-infected individuals attending ART clinics in rural Nakaseke district of Uganda. We enrolled HIV-positive participants from four HIV treatment centers in rural Uganda. Participants underwent spirometry testing following standard guidelines. We defined COPD as a post-bronchodilator FEV 1 /FVC ratio less than the fifth percentile of the NHANES III African-American reference. We assessed for factors associated with COPD and lung function profiles using multivariable logistic and linear regression analyses. We analyzed data from 722 HIV-positive participants (mean age 48.0 years, 59.7% women). Over 90% of participants were on ART for a median duration of 4 years (IQR 2-7 years), with a median viral load of 0 copies/mL (IQR 0-0 copies/mL), current and baseline CD4 + T cell count of 478 cells/mm 3 (IQR 346-663 cells/mm 3 ) and 335 cells/mm 3 (IQR 187-523 cells/mm 3 ) respectively. The prevalence of COPD was 6.22%. COPD was associated with worse respiratory symptoms and health status. History of pulmonary tuberculosis was strongly associated with COPD (adjusted OR = 4.92, 95% CI 1.71 to 14.15, p = 0.003) and reduced lung function. Use of ART, CD 4 +T cell count and viral load were not associated with COPD or reduced lung function. In conclusion, we report a COPD prevalence of 6.22% in HIV-infected individuals in rural Uganda. Pulmonary tuberculosis remains the strongest predictor of COPD risk and reduced lung function in well-controlled HIV

24-hour ambulatory blood pressure monitoring and hypertension related risk among HIV-positive and HIV-negative individuals: cross sectional study findings from rural Uganda

Hypertension is diagnosed and treated based on blood pressure (BP) readings obtained in the clinic setting. Positive HIV status is associated with a higher prevalence of abnormal diurnal BP patterns, diagnosed with ambulatory BP monitoring rather than the conventional method of BP measurement. Little is known about ambulatory BP profiles in people living with HIV (PLHIV) in low-income countries, especially within sub-Saharan Africa. In this study, we compared 24-h ambulatory BP profiles of 140 HIV-positive individuals vs. profiles in 166 HIV negative individuals living in rural Uganda. HIV was well-controlled, with all HIV seropositive participants reporting use of anti-retroviral therapy, and ~123 (88%) having undetectable viral load. Most participants reported ART use duration of less than 10 years. Compared to HIV negative participants, HIV positive participants had lower median 24-h systolic BP (110.4 mmHg (IQR: 105.7, 118.7) vs 117.7 mmHg (IQR: 110.8, 129.8), p < 0.001), and 24-h diastolic BP (69.2 mmHg (IQR: 65.0, 74.9) vs. 71.9 mmHg (IQR: 67.2, 78.1), p = 0.004). Adjusted results showed greater percentage systolic nocturnal dipping among PLHIV compared to HIV negative individuals (difference = 2.70 (IQR: 0.94, 4.47), p < 0.05). Results of the adjusted Poisson regression suggested lower prevalence of 24-h and night hypertension among HIV positives compared to HIV negative, but were not statistically significant. Our data suggest that continuous 24-h BP measurements are lower in PLHIV on ART compared to HIV negative individuals