Comparison of methods for the analysis of airway macrophage particulate load from induced sputum, a potential biomarker of air pollution exposure.

BACKGROUND Air pollution is associated with a high burden or morbidity and mortality, but exposure cannot be quantified rapidly or cheaply. The particulate burden of macrophages from induced sputum may provide a biomarker. We compare the feasibility of two methods for digital quantification of airway macrophage particulate load. METHODS Induced sputum samples were processed and analysed using ImageJ and Image SXM software packages. We compare each package by resources and time required. RESULTS 13 adequate samples were obtained from 21 patients. Median particulate load was 0.38 μm(2) (ImageJ) and 4.0 % of the total cellular area of macrophages (Image SXM), with no correlation between results obtained using the two methods (correlation coefficient = -0.42, p = 0.256). Image SXM took longer than ImageJ (median 26 vs 54 mins per participant, p = 0.008) and was less accurate based on visual assessment of the output images. ImageJ's method is subjective and requires well-trained staff. CONCLUSION Induced sputum has limited application as a screening tool due to the resources required. Limitations of both methods compared here were found: the heterogeneity of induced sputum appearances makes automated image analysis challenging. Further work should refine methodologies and assess inter- and intra-observer reliability, if these methods are to be developed for investigating the relationship of particulate and inflammatory response in the macrophage

Household Air Pollution and Acute Lower Respiratory Infections in Adults: A Systematic Review.

INTRODUCTION: Household air pollution from solid fuel burning kills over 4 million people every year including half a million children from acute lower respiratory infections. Although biologically plausible, it is not clear whether household air pollution is also associated with acute lower respiratory infections in adults. We systematically reviewed the literature on household air pollution and acute lower respiratory infection in adults to identify knowledge gaps and research opportunities. METHODS: Ten bibliographic databases were searched to identify studies of household air pollution and adult acute lower respiratory infection. Data were extracted from eligible studies using standardised forms. RESULTS: From 4617 titles, 513 abstracts and 72 full-text articles were reviewed. Eight studies met the inclusion criteria of which 2 found a significant adjusted increased risk of acute lower respiratory infection, 2 identified a univariate association whilst 4 found no significant association. Study quality was generally limited. Heterogeneity in methods and findings precluded meta-analysis. DISCUSSION: A systematic review of the literature found limited evidence for an association between household air pollution and risk of acute lower respiratory infection in adults. Additional research, with carefully defined exposure and outcome measures, is required to complete the risk profile caused by household air pollution in adults. REGISTRATION NUMBER: CRD42015028042

Study protocol: the effects of air pollution exposure and chronic respiratory disease on pneumonia risk in urban Malawian adults - the Acute Infection of the Respiratory Tract Study (The AIR Study)

Background Pneumonia is the 2nd leading cause of years of life lost worldwide and is a common cause of adult admissions to hospital in sub-Saharan Africa. Risk factors for adult pneumonia are well characterised in developed countries, but are less well described in sub-Saharan Africa where HIV is a major contributing factor. Exposure to indoor and outdoor air pollution is high, and tobacco smoking prevalence is increasing in sub-Saharan Africa, yet the contribution of these factors to the burden of chronic respiratory diseases in sub-Saharan Africa remains poorly understood. Furthermore, the extent to which the presence of chronic respiratory diseases and exposure to air pollution contribute to the burden of pneumonia is not known. Design The Acute Infection of the Respiratory Tract Study (The AIR Study) is a case–control study to identify preventable risk factors for adult pneumonia in the city of Blantyre, Malawi. Cases will be adults admitted with pneumonia, recruited from Queen Elizabeth Central Hospital, the largest teaching hospital in Malawi. Controls will be adults without pneumonia, recruited from the community. The AIR Study will recruit subjects and analyse data within strata defined by positive and negative HIV infection status. All participants will undergo thorough assessment for a range of potential preventable risk factors, with an emphasis on exposure to air pollution and the presence of chronic respiratory diseases. This will include collection of questionnaire data, clinical samples (blood, urine, sputum and breath samples), lung function data and air pollution monitoring in their home. Multivariate analysis will be used to identify the important risk factors contributing to the pneumonia burden in this setting. Identification of preventable risk factors will justify research into the effectiveness of targeted interventions to address this burden in the future. Discussion The AIR Study is the first study of radiologically confirmed pneumonia in which air pollution exposure measurements have been undertaken in this setting, and will contribute important new information about exposure to air pollution in urban SSA. Through identification of preventable risk factors, the AIR Study aims to facilitate future research and implementation of targeted interventions to reduce the high burden of pneumonia in SSA

Pneumococcal vaccination coverage among children with sickle cell anemia, sickle cell trait, and normal hemoglobin

BackgroundChildren with sickle cell anemia and sickle cell trait are at an increased risk of invasive pneumococcal disease compared to children with normal hemoglobin. We assessed and compared pneumococcal vaccination status among these three groups.ProcedureChildren with sickle cell anemia and sickle cell trait were identified using Michigan newborn screening records (1997–2014); each child was matched to four children with normal hemoglobin based on age, Medicaid enrollment (at least 1 year from 2012–2014), race, and census tract. Vaccination records were obtained from the state’s immunization system. Pneumococcal vaccine coverage (PCV7 or PCV13 depending on date of administration) was assessed at milestone ages of 3, 5, 7, and 16 months. The proportion of children with vaccine coverage at each milestone was calculated overall and compared among children with sickle cell anemia, sickle cell trait, and normal hemoglobin using chi‐square tests.ResultsThe study population consisted of 355 children with sickle cell anemia, 17,319 with sickle cell trait, and 70,757 with normal hemoglobin. The proportion of children with age‐appropriate pneumococcal vaccination coverage was low at each milestone and generally decreased over time. Children with sickle cell anemia were more likely to be covered compared to children with sickle cell trait or normal hemoglobin.ConclusionsDespite higher pneumococcal vaccination coverage among children with sickle cell anemia, opportunities for improvement exist among all children. Targeted interventions will benefit from mechanisms to identify children with increased risks such as sickle cell anemia or trait to improve pneumococcal vaccination coverage among these groups.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145560/1/pbc27282.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145560/2/pbc27282_am.pd

Hydroxyurea use among children with sickle cell anemia

This study describes hydroxyurea use among children ages 1 to 17 with sickle cell anemia (SCA) enrolled in at least one year of Medicaid in six states from 2005 to 2012. Administrative claims were used to summarize the number of days’ supply of hydroxyurea dispensed by state and year. A total of 7963 children with SCA contributed 22 424 person‐years. Among person‐years with greater than 30 days of hydroxyurea, only 18% received at least 300 days of hydroxyurea, which varied by state. Following updated recommendations for all children with SCA to be offered hydroxyurea, strategies to increase hydroxyurea adherence among this population are needed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149259/1/pbc27721_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149259/2/pbc27721.pd

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

Household air pollution, chronic respiratory disease and pneumonia in Malawian adults: A case-control study

Background: Four million people die each year from diseases caused by exposure to household air pollution. There is an association between exposure to household air pollution and pneumonia in children (half a million attributable deaths a year); however, whether this is true in adults is unknown. We conducted a case-control study in urban Malawi to examine the association between exposure to household air pollution and pneumonia in adults. Methods: Hospitalized patients with radiologically confirmed pneumonia (cases) and healthy community controls underwent 48 hours of ambulatory and household particulate matter (µg/m3) and carbon monoxide (ppm) exposure monitoring. Multivariate logistic regression, stratified by HIV status, explored associations between these and other potential risk factors with pneumonia. Results: 145 (117 HIV-positive; 28 HIV-negative) cases and 253 (169 HIV-positive; 84 HIV-negative) controls completed follow up. We found no evidence of association between household air pollution exposure and pneumonia in HIV-positive (e.g. ambulatory particulate matter adjusted odds ratio [aOR] 1.00 [95% CI 1.00–1.01, p=0.141]) or HIV-negative (e.g. ambulatory particulate matter aOR 1.00 [95% CI 0.99–1.01, p=0.872]) participants. Chronic respiratory disease was associated with pneumonia in both HIV-positive (aOR 28.07 [95% CI 9.29–84.83, p<0.001]) and HIV-negative (aOR 104.27 [95% CI 12.86–852.35, p<0.001]) participants. Conclusions: We found no evidence that exposure to household air pollution is associated with pneumonia in Malawian adults. In contrast, chronic respiratory disease was strongly associated with pneumonia

Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza Illness in Malawian Adults:A Prospective Cohort and Parallel Case-Control Study

The impact of HIV infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings, but is rarely implemented in Africa.We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized lower respiratory tract infection (LRTI)), and mild influenza (influenza-like illness (ILI)).The cohort study enrolled 608 adults (360 (59%) HIV-infected). Between April 2013 and March 2015, 24/229 (10.5%) ILI episodes in HIV-infected and 5/119 (4.2%) in HIV-uninfected adults were influenza PCR positive (incidence rates 46.0 vs. 14.5 per 1000 person years, incidence rate ratio 2.75; 95% confidence interval [CI] 1.02-7.44; p=0.03, adjusted for age, gender, household crowding and food security). In the case control study, influenza was identified in 56/518 (10.8%) patients with hospitalized LRTI, and 88/642 (13.7%) with ILI. HIV prevalence among influenza-positive cases and controls were 69.6% and 29.6% respectively. HIV was a significant risk factor for severe influenza (odds ratio 4.98, 95%CI 2.09-11.88, p<0.001; population attributable fraction 57%, adjusted for season, sanitation facility and food security).HIV is an important risk factor for influenza-associated ILI and severe presentation in this high HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be re-evaluated and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined