Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function. METHODS: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis. RESULTS: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC

Prevalence and determinants of chronic respiratory diseases in adults in rural Sudan.

BACKGROUND: Chronic respiratory diseases (CRDs) greatly contribute to worldwide mortality. Despite new data emerging from Africa, prevalence estimates and determinants of CRDs in rural settings are limited. This study sought to extend the existing research conducted in urban Sudan by conducting a rural comparison.METHODS: Participants aged ≥18 years (n = 1,850), living in rural Gezira State completed pre-and post-bronchodilator spirometry and a questionnaire. Prevalence of respiratory symptoms and spirometric abnormalities were reported. Regression analyses were used to identify risk factors for CRDs.RESULTS: Prevalence of chronic airflow obstruction (CAO) was 4.1% overall and 5.5% in those aged ≥40 years. Reversibility was seen in 6.4%. Low forced vital capacity (FVC) was seen in 58.5%, and at least one respiratory symptom was present in 40.7% of the participants. CAO was more common among people aged 60-69 years (OR 2.07, 95% CI 1.13-3.82) and less common among highly educated participants (OR 0.50, 95% CI 0.27-0.93). Being underweight was associated with lower FVC (OR 3.07, 95% CI 2.24-4.20).CONCLUSIONS: A substantial burden of CRD exists among adults in rural Sudan. Investment in CRD prevention and management strategies is needed.

Prevalence and determinants of chronic respiratory diseases in adults in Sudan.

BACKGROUND: Chronic respiratory diseases (CRDs) are considered a significant cause of morbidity and mortality worldwide, although data from Africa are limited. This study aimed to determine the prevalence and determinants of CRDs in Khartoum, Sudan.METHODS: Data were collected from 516 participants aged ≥40 years, who had completed a questionnaire and undertook pre- and post-bronchodilator spirometry testing. Trained field workers administered the questionnaires and conducted spirometry. Survey-weighted prevalence of respiratory symptoms and spirometric abnormalities were estimated. Regression analysis models were used to identify risk factors for chronic lung diseases.RESULTS: Using the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) reference equations, the prevalence of chronic airflow obstruction (CAO) was 10%. The main risk factor was older age, 60-69 years (OR 3.16, 95% CI 1.20-8.31). Lower education, high body mass index and a history of TB were also identified as significant risk factors. The prevalence of a low forced vital capacity (FVC) using NHANES III was 62.7% (SE 2.2) and 11.3% (SE 1.4) using locally derived values.CONCLUSION: The prevalence of spirometric abnormality, mainly low FVC, was high, suggesting that CRD is of substantial public health importance in urban Sudan. Strategies for the prevention and control of these problems are needed.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Post-tuberculosis lung health: perspectives from the First International Symposium.

ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1st International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on a toolkit for future PTLD measurement and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.

The locus C11orf30 increases susceptibility to poly-sensitization.

A number of genetic variants have been associated with allergic sensitization, but whether these are allergen specific or increase susceptibility to poly-sensitization is unknown. Using data from the large multicentre population-based European Community Respiratory Health Survey, we assessed the association between 10 loci and specific IgE and skin prick tests to individual allergens and poly-sensitization. We found that the 10 loci associate with sensitization to different allergens in a nonspecific manner and that one in particular, C11orf30-rs2155219, doubles the risk of poly-sensitization (specific IgE/4 allergens: OR = 1.81, 95% CI 0.80-4.24; skin prick test/4+ allergens: OR = 2.27, 95% CI 1.34-3.95). The association of rs2155219 with higher levels of expression of C11orf30, which may be involved in transcription repression of interferon-stimulated genes, and its association with sensitization to multiple allergens suggest that this locus is highly relevant for atopy.

LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk.

BACKGROUND: Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors. METHODS: Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed. RESULTS: The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99-1.60, P=0.06) and 1.33 (95% CI 1.05-1.69, P=0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interaction<0.05). CONCLUSIONS: The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer.

Exposure of thermoelectric power-plant workers to volatile organic compounds from fuel oil: genotoxic and cytotoxic effects in buccal epithelial cells.

Thermoelectric power-plant workers are constantly exposed to high levels of potentially genotoxic gaseous substances, such as volatile organic compounds (VOCs) from the combustion of fuel oil or the processing of naphtha. The aim of the present study was to estimate the association between such occupational exposure and the frequency of micronucleated cells and cells with other nuclear anomalies. Buccal epithelial cells were collected from a total of 44 power-plant workers (exposed group) and 47 administrative workers (non-exposed group), and examined for the frequency of micronucleated cells (MNC) and of cells with other nuclear anomalies (ONA: pyknosis, karyolysis, and karyorrhexis) by means of the micronucleus assay. The frequencies of MNC and ONA per 1000 cells in the exposed group (1.8‰ and 82.4‰, respectively) were significantly higher than in the non-exposed group (0.2‰ and 58.3‰, respectively). The exposed group had a twelve-fold increase in risk for formation of MNC compared with non-exposed individuals (RR=12.1; 95% CI, 5.0-29.2; P<0.001). The confounding factors analyzed (age, smoking status, alcohol consumption, and mouthwash use) did not show any significant association with the frequency of MNC or ONA. The findings of this study show that workers from power plants exposed to VOCs have a significantly elevated risk for DNA damage. Therefore, bio-monitoring of DNA damage is recommended for this group of workers.

Prevalence of Calodium hepaticum (Syn. Capillaria hepatica) in house mice (Mus musculus) in the Azores archipelago.

Calodium hepaticum (Syn. Capillaria hepatica) is a zoonotic liver nematode of mammals distributed worldwide. Rodents are believed to be the main reservoirs of this nematode. In this paper, prevalence of the parasite was analyzed in liver histological sections from 51 house mice (Mus musculus) caught in human-inhabited houses, from two localities (Furnas and Rabo de Peixe) on São Miguel island from the Azores archipelago (Portugal). Mean prevalence of infection was 19.6%, with 33.3% prevalence in Furnas and 4.1% in Rabo de Peixe (P=0.07). No significant differences were found between the prevalence of infection and the age, body weight and the sex of mice. Hepatic lesions found were either acute and/or chronic stage and consisted of moderate to severe multifocal pyogranulomatous hepatitis with encapsulated eggs with typical bipolar plugs and moderate to severe necrotizing hepatitis consistent with larva tracks. Periportal inflammatory infiltration, hepatocyte regeneration and bile duct hyperplasia were also noted. In most cases, hepatic lesions occupied more than 50% of the liver, but despite severe lesions, in some mice, no signs of hepatic failure were noticed. The high rate of infection found in the present study suggests that house mice are an important reservoir for this parasite in the Azores and could have a role in human transmission.

Autometallography and metallothionein immunohistochemistry in hepatocytes of turbot (Scophthalmus maximus L.) after exposure to cadmium and depuration treatment.

In this study, autometallography and immunohistochemistry were used to localize and quantify cadmium and metallothionein (MT) levels, respectively, in cellular compartments of turbot liver on exposure to cadmium for 7 days and further depuration treatment for 14 days. Metals weakly bound to proteins (i.e. MTs) in hepatocyte lysosomes were visualized as black silver deposits (BSDs) using a light microscope. With the aid of a newly developed immunohistochemical procedure, MTs were localized and semi-quantified in both the cytosolic and the lysosomal compartments of hepatocytes. The BSD extent in the lysosomes of hepatocytes increased significantly as a result of cadmium exposure. This response was evidenced after 1 h. Further, a progressive increase in the volume density of BSDs occurred up to the seventh day. Total MT immunohistochemical levels increased at a lower rate, starting after 1 day of cadmium exposure. BSD extent values recovered after depuration, whilst MT levels remain unchanged. It is possible that the detoxification rate of metals via lysosomes was diminished, whilst MT levels remained unchanged, at least after 14 days of depuration. It can be concluded that autometallography and MT immunohistochemistry are good tools for clarifying metal and metal-MT trafficking routes in hepatocytes, and also that BSD extent and MT immunohistochemical levels in the lysosomes and cytosol of fish hepatocytes can be considered to be useful biomarkers of metal exposure.