Kevin Mortimer

Respiratory risks from household air pollution in low and middle income countries

A third of the worlds population uses solid fuel derived from plant material (biomass) or coal for cooking, heating, or lighting. These fuels are smoky, often used in an open fire or simple stove with incomplete combustion, and result in a large amount of household air pollution when smoke is poorly vented. Air pollution is the biggest environmental cause of death worldwide, with household air pollution accounting for about 3·5-4 million deaths every year. Women and children living in severe poverty have the greatest exposures to household air pollution. In this Commission, we review evidence for the association between household air pollution and respiratory infections, respiratory tract cancers, and chronic lung diseases. Respiratory infections (comprising both upper and lower respiratory tract infections with viruses, bacteria, and mycobacteria) have all been associated with exposure to household air pollution. Respiratory tract cancers, including both nasopharyngeal cancer and lung cancer, are strongly associated with pollution from coal burning and further data are needed about other solid fuels. Chronic lung diseases, including chronic obstructive pulmonary disease and bronchiectasis in women, are associated with solid fuel use for cooking, and the damaging effects of exposure to household air pollution in early life on lung development are yet to be fully described. We also review appropriate ways to measure exposure to household air pollution, as well as study design issues and potential effective interventions to prevent these disease burdens. Measurement of household air pollution needs individual, rather than fixed in place, monitoring because exposure varies by age, gender, location, and household role. Women and children are particularly susceptible to the toxic effects of pollution and are exposed to the highest concentrations. Interventions should target these high-risk groups and be of sufficient quality to make the air clean. To make clean energy available to all people is the long-term goal, with an intermediate solution being to make available energy that is clean enough to have a health impact.

Experimental hookworm infection: a randomized placebo-controlled trial in asthma

Background Epidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma.

Quadrupling the Dose of Inhaled Corticosteroid to Prevent Asthma Exacerbations A Randomized, Double-blind, Placebo-controlled, Parallel-Group Clinical Trial

RATIONALE Asthma exacerbations are unpredictable, disruptive, and frightening, and are therefore important to prevent. OBJECTIVES We investigated whether a policy of quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate reduces asthma exacerbations requiring treatment with oral corticosteroids. METHODS A total of 403 people with asthma were given a self-management plan and randomized to take an active or placebo corticosteroid inhaler in addition to their usual asthma treatment when their PEF fell by 15% on 2 consecutive days or by 30% on 1 day. The study inhalers provided a quadrupling or no change in corticosteroid dose. MEASUREMENTS AND MAIN RESULTS Eighteen of 197 (9%) and 29 of 203 (14%) participants had an exacerbation of asthma requiring treatment with oral corticosteroids in the active and placebo groups, respectively, giving a risk ratio of 0.64 (95% confidence interval, 0.37-1.11, P = 0.11). Of the 94 participants who started the study inhaler far fewer required treatment with oral corticosteroids in the active compared with the placebo group: 12 of 56 (21%) in the active group and 19 of 38 (50%) in the placebo group, giving a risk ratio of 0.43 (95% confidence interval, 0.24-0.78, P = 0.004). CONCLUSIONS Although our primary outcome did not reach statistical significance, quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate appears to reduce acute exacerbations of asthma and deserves further investigation. Clinical trial registered with www.controlled-trials.com (ISRCTN 46018181).

Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study

Background Epidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration.

Oral and inhaled corticosteroids and adrenal insufficiency: a case-control study

Background: Adrenal insufficiency, a well recognised complication of treatment with oral corticosteroids, has been described in association with inhaled corticosteroid use in over 60 case reports. The risk of adrenal insufficiency in people prescribed an oral or inhaled corticosteroid in the general population is not known. A study was undertaken to quantify the association between adrenal insufficiency and oral and inhaled corticosteroid exposure. Methods: A case-control study was performed using computerised general practice data from The Health Improvement Network. Results: From a cohort of 2.4 million people, 154 cases of adrenal insufficiency and 870 controls were identified. There was a dose related increased risk of adrenal insufficiency in people prescribed an oral corticosteroid with an odds ratio of 2.0 (95% CI 1.6 to 2.5) per course of treatment per year. Adrenal insufficiency was associated with a prescription for an inhaled corticosteroid during the 90 day period before the diagnosis with an odds ratio of 3.4 (95% CI 1.9 to 5.9) and this effect was dose related (p for trend <0.001). After adjusting for oral corticosteroid exposure, this odds ratio was reduced to 1.6 (95% CI 0.8 to 3.2) although the dose relation remained (p for trend 0.036). Conclusion: People prescribed an oral or inhaled corticosteroid are at a dose related increased risk of adrenal insufficiency although the absolute risk is small. This analysis suggests that the increased risk in people prescribed an inhaled corticosteroid is largely due to oral corticosteroid exposure, but inhaled corticosteroids may have an effect when they are taken at higher doses.

Household air pollution is a major avoidable risk factor for cardiorespiratory disease.

Household air pollution (HAP) from biomass fuels, coal, and kerosene burned in open fires, primitive stoves, and lamps causes at least 2 million deaths per year. Many of these deaths occur in children <5 years of age with pneumonia and in women with COPD, lung cancer, and cardiovascular disease. HAP is inextricably linked to poverty, with activities to obtain fuel consuming a large proportion of the time and financial resources of poor households. Thus, fewer resources used in this way means less is available for basic needs like food, education, and health care. The burden of work and the exposure to smoke, particularly during cooking, are predominantly borne by women and children. Although historically HAP has not received sufficient attention from the scientific, medical, public health, development, and policy-making communities, the tide has clearly changed with the broad-based support and launch of the Global Alliance for Clean Cookstoves in 2010. There is now considerable reason for optimism that this substantial cause of cardiorespiratory morbidity and mortality will be addressed comprehensively and definitively. Drawing on our experience from four continents, we provide background information on the problem of HAP, health impacts of HAP, opportunities for research, and the current best solutions.

Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?

BACKGROUND Poor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success. AIM To determine whether treatment with a single inhaler containing a long-acting beta(2)-agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids. DESIGN OF STUDY Randomised, parallel group, open-label trial. SETTING Forty-four general practices in Nottinghamshire. METHOD Participants who used less than 70% of their prescribed dose of inhaled corticosteroid and had poorly controlled asthma were randomised to budesonide 200 microg one puff twice daily plus their own short-acting beta(2)-agonist as required (control group), or budesonide/formoterol 200/6 microg one puff once daily and as required (active group) for 6 months. The primary outcome was inhaled corticosteroid dose. RESULTS Seventy-one participants (35 control, 36 active group) were randomised. Adherence with budesonide in the control group was approximately 60% of the prescribed dose. Participants in the active group used approximately 80% more budesonide than participants in the control group (448 versus 252 microg/day, mean difference 196 mug, 95% confidence interval 113 to 279; P<0.001) and were less likely to withdraw from the study (3 versus 13; P<0.01). No safety issues were identified. CONCLUSION Using a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken, suggesting this could be a useful strategy to overcome the problems related to poor adherence with inhaled corticosteroids.

Effects of inhaled corticosteroids on bone

OBJECTIVE To discuss the effects of inhaled corticosteroids on bone and their potential public health implications. DATA SOURCES The MEDLINE and EMBASE databases were searched to identify articles published between 1966 and January 2004 with the following keywords in the title: inhaled corticosteroid, beclomethasone, budesonide, flunisolide, fluticasone, mometasone, triamcinolone plus bone, fracture, osteoporosis, osteocalcin, growth, or height. STUDY SELECTION Key studies of adequate size and duration that allowed for potential confounding factors where required were selected. RESULTS Inhaled corticosteroids are absorbed into the systemic circulation and therefore have the potential to cause adverse effects on bone. Several of the larger studies showed that inhaled corticosteroids cause a dose-related reduction in bone mineral density. Three cross-sectional studies found a dose-related increase in fractures in people taking an inhaled corticosteroid compared with controls. Prospective studies found a short-term reduction in growth velocity in children taking an inhaled corticosteroid, although target adult height is usually achieved. CONCLUSION Since osteoporotic fracture is common in elderly patients and up to 5% of the population in more developed countries take an inhaled corticosteroid, these findings have public health implications. Strategies are needed to reduce the systemic effects of inhaled corticosteroids.

Household Air Pollution Causes Dose-dependent Inflammation and Altered Phagocytosis in Human Macrophages

Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by IL-6 and IL-8 production in response to particulate challenge; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte-derived macrophages. Fine carbon black induced IL-8 release from monocyte-derived and alveolar macrophages (P < 0.05) with similar magnitude responses (log10 increases of 0.93 [SEM = 0.2] versus 0.74 [SEM = 0.19], respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (P = 0.0015). There was no overall effect on killing of M. tuberculosis. Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke-exposed cells demonstrate reduced phagocytosis, but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions.

Chronic obstructive pulmonary disease in sub-Saharan Africa: a systematic review.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a major global health problem. Although COPD is the sixth most common cause of mortality in low- and middle-income countries, most research comes from high-income countries. We set out to systematically review existing published research on COPD in sub-Saharan Africa to identify knowledge gaps and opportunities for further research. METHODS A literature search of MEDLINE, EMBASE and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases, published reviews, reference lists from included publications and abstracts from major thoracic medicine conference proceedings within the previous 2 years was performed using a protocol-driven search strategy. Texts were screened for inclusion by two independent reviewers. Studies were included if they met the following criteria: 1) COPD was an outcome, and 2) the population included people from sub-Saharan Africa. There were no language restrictions. FINDINGS Our search identified 688 studies: 41 were duplicates, 638 were excluded, and 9 met our inclusion criteria. Included studies were all cross-sectional, and included 3673 people from four sub-Saharan African countries. Estimates of COPD prevalence varied between 4% and 25%. Only one study used population-based representative sampling and an adequate case definition. Assessment of risk factors was limited. CONCLUSIONS There is little existing research on COPD in sub-Saharan Africa. Prevalence estimates varied, reflecting the range of populations studied, inconsistent diagnostic criteria and variable methods and methodological quality. Population-representative studies using appropriate case definitions are needed to define the epidemiology of COPD in sub-Saharan Africa and to inform the development of prevention and management strategies for the future.