Search

We applied data from a population-based prospective study, the Espoo Cohort Study (n = 2,568), to identify the potential susceptibility of persons with asthma to respiratory tract infections (RTIs). Information on the occurrence of asthma and both upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) was collected with a questionnaire at baseline and at the 6-year and 20-year follow-up studies, and from the Finnish national health registries. We estimated age- and sex-specific incidence rate differences (IRDs) and incidence rate ratios (IRRs) by applying negative binomial regression. Meta-regression was used to summarize the age-specific IRRs from childhood to 27 years of age. Individuals with asthma at any age during the follow-up period had increased risks of both URTIs (adjusted IRD = 72.6 (95% confidence interval (CI): 50.6, 94.7) per 100 person-years; adjusted IRR = 1.27 (95% CI: 1.20, 1.35)) and LRTIs (adjusted IRD = 25.5 (95% CI: 17.9, 33.1); adjusted IRR = 2.87 (95% CI: 2.33, 3.53)) from childhood to young adulthood. In young adulthood, the association between asthma and URTIs was stronger in women than in men, while such an association was not detected for LRTIs. This analysis provides strong evidence that persons with asthma experience more RTIs from preschool age to young adulthood than do those without asthma. Thus, they constitute a susceptible population for RTIs. Women with asthma are at especially high risk.

Previous studies have provided contradictory evidence on the role of early childhood respiratory infections in the development of asthma and other allergic diseases during childhood. We investigated early-life respiratory infections as predictors of the development of asthma in a 20-year prospective cohort study (the Espoo Cohort Study, 1991-2011). Information on upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) was collected with a parent-administered baseline questionnaire covering the preceding 12 months (part 1; n = 2,228), and information on LRTIs leading to hospitalization was obtained from the National Hospital Discharge Registry (part 2; n = 2,568). The incidence of asthma was assessed on the basis of 6-year and 20-year follow-up questionnaires. Adjusted hazard ratios were estimated using Cox proportional hazards models. Both URTIs (adjusted hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.22, 2.19) and LRTIs (adjusted HR = 2.11, 95% CI: 1.48, 3.00) in early childhood were strong predictors of asthma incidence up to young adulthood (ages 20-27 years). A declining age trend was present for both URTIs (P-trend < 0.01) and LRTIs (P-trend < 0.001). In part 2 of our analysis, a significant risk of asthma was found in relation to LRTIs requiring hospitalization (adjusted HR = 1.93, 95% CI: 1.10, 3.38). The results provide new evidence that respiratory tract infections in early life predict the development of asthma through childhood to young adulthood.

Diurnal variation (DV) affects lung function but the changes are thought to be related to sleep patterns rather than time of day. When diagnosing occupational asthma (OA), serial peak expiratory flow (PEF) measurements are the recommended first line investigation, but could be confounded by shift work.The aim of the study was to investigate the effects of shift work on PEF measurements used for diagnosing OA.PEF records containing more than one shift pattern with ≥ 4 days per shift were identified. OA diagnosis was based on an Oasys-2 score ≥ 2.51 and non-OA on having an alternative clinical diagnosis and Oasys-2 score2.51. The mean area between curves (ABC) score, mean PEF DV and cross-shift PEF changes were calculated for each shift.Records from 123 workers with OA and 69 without OA satisfied inclusion criteria. In the OA group, PEF declined more on afternoon and night shifts than days (P0.001). The ABC score was lower in the OA group on night (P0.05) and afternoon shifts (P0.05) as compared with days, without significant differences in DV. Among those without OA, cross-shift PEF increased more on day shifts (mean + 25 l/min) than afternoon or night shifts (+1 l/min) (P0.001). The sensitivity for the ABC score and DV were good and similar across shifts, but specificity was reduced using DV (DV mean 39%; ABC 98%).PEF responses between work and rest show small differences according to shift type. The ABC score has a high sensitivity and specificity for all shifts; differences in DV have lower specificity.

We present a method, LineageProgram, that uses the developmental lineage relationship of observed gene expression measurements to improve the learning of developmentally relevant cellular states and expression programs. We find that incorporating lineage information allows us to significantly improve both the predictive power and interpretability of expression programs that are derived from expression measurements from in vitro differentiation experiments. The lineage tree of a differentiation experiment is a tree graph whose nodes describe all of the unique expression states in the input expression measurements, and edges describe the experimental perturbations applied to cells. Our method, LineageProgram, is based on a log-linear model with parameters that reflect changes along the lineage tree. Regularization with L1 that based methods controls the parameters in three distinct ways: the number of genes change between two cellular states, the number of unique cellular states, and the number of underlying factors responsible for changes in cell state. The model is estimated with proximal operators to quickly discover a small number of key cell states and gene sets. Comparisons with existing factorization, techniques, such as singular value decomposition and non-negative matrix factorization show that our method provides higher predictive power in held, out tests while inducing sparse and biologically relevant gene sets., National Institutes of Health (U.S.) (P01-NS055923), National Institutes of Health (U.S.) (1-UL1-RR024920)

There is inconclusive evidence suggesting a possible association of asthma with increased risk of caries. The authors conducted a systematic review and meta-analysis to synthesize the evidence on the relation between asthma and caries. They performed an Ovid Medline (US National Library of Medicine) database search of literature published from 1950 through May 2010 using the Medical Subject Headings "asthma" and "caries." Summary effect estimates were calculated with fixed- and random-effects models, and determinants of heterogeneity were studied in meta-regression analysis. The meta-analysis was based on 11 articles providing estimates of the effect of asthma on primary dentition and 14 articles on permanent dentition. Summary effect estimates for the relation between asthma and caries from the random-effects models were 2.73 (95% confidence interval: 1.61, 4.64) and 2.04 (95% confidence interval: 1.44, 2.89), respectively. Factors identified as determinants of heterogeneity were geographic region for primary dentition and publication year, sample size, asthma definition, and information on the use of asthma medication for permanent dentition. Evidence from this analysis suggests that asthma doubles the risk of caries in both primary and permanent dentition. Publication bias diagnostics and simulation suggested possible overestimation of the summary odds ratio for permanent dentition but not for primary dentition. Physicians and dentists should recommend preventive measures against caries for persons with asthma.

The authors assessed the relation between exposure to dampness and molds in dwellings and the development of allergic rhinitis in childhood in a 6-year, population-based prospective cohort study of 1,863 children aged 1-7 years at baseline in 1991 (follow-up rate, 77%) from Espoo, Finland. The studied exposures were history of water damage, presence of moisture and visible mold, and perceived mold odor in the home, based on parent-administered questionnaire. A total of 246 (13.2%) children developed physician-diagnosed allergic rhinitis during the study period, resulting in an incidence rate of 440 cases per 10,000 person-years (95% confidence interval (CI): 387, 499). In logistic regression adjusting for confounding, any mold or dampness exposure indicator at baseline (adjusted odds ratio = 1.55, 95% CI: 1.10, 2.18), at follow-up (adjusted odds ratio = 1.62, 95% CI: 1.21, 2.18), or both (adjusted odds ratio = 1.96, 95% CI: 1.29, 2.98) was an important independent determinant of the risk of allergic rhinitis. Of the individual indicators, water damage and moisture on the surfaces were consistent determinants of allergic rhinitis. The results of this cohort study, which assessed exposure before the onset of allergic rhinitis, strengthen considerably the evidence of the role of indoor dampness problems as determinants of allergic rhinitis in children.

The Oasys programme plots serial peak expiratory flow (PEF) measurements and produces scores of the likelihood that the recordings demonstrate occupational asthma. We have previously shown that the area between the mean workday and rest day PEF curves [the area between the curves (ABC) score] has a sensitivity of 69% and specificity of 100% when plotted from waking time using a cut-off score of 15 l/min/h.To investigate the minimum data requirements to maintain the sensitivity and specificity of the ABC score.A total of 196 sets of measurements from workers with occupational asthma confirmed by methods other than serial PEFs and 206 records from occupational and non-occupational asthmatics who were not at work at the time of PEF monitoring were analysed according to their mean number of readings per day. Measurements from work and rest days were sequentially removed separately and the ABC score calculated at each reduction. The sensitivity and specificity of the ABC score (using a cut-off of 15 l/min/h) was calculated for each duration.Two-hourly measurements (approximately 8 readings per day) with eight workdays and three rest days had 68% sensitivity and 91% specificity for occupational asthma diagnosis. As readings decreased toor=4 readings per day,or=15 workdays were required to provide a specificity above 90%.To be sensitive and specific in the diagnosis of occupational asthma, the ABC score requires 2-hourly PEF measurements on eight workdays and three rest days. This is a short assessment period that should improve patient compliance.

BACKGROUND Trends of occupational asthma (OA) differ between regions depending on local industries, provisions for health and safety at the workplace and the availability of a reporting scheme to help in data collection and interpretation. AIM To assess trends in OA in an industrialized part of the UK over a 15-year period. METHODS Occupational and chest physicians in the West Midlands were invited to submit details of newly diagnosed cases with OA. Data were then transferred to the regional centre for occupational lung diseases for analysis. RESULTS A total of 1461 cases were reported to the scheme. Sixty-eight per cent were males with mean (standard deviation) age of 44 (12) years. The annual incidence of OA was 42 per million of working population (95% CI = 37-45). OA was most frequently reported in welders (9%) and health care-related professions (9%) while < 1% of cases were reported in farmers. Isocyanates were the commonest offending agents responsible for 21% of reports followed by metal working fluids (MWFs) (11%), adhesives (7%), chrome (7%), latex (6%) and glutaraldehyde (6%). Flour was suspected in 5% of cases while laboratory animals only in 1%. CONCLUSIONS Our data confirm a high annual incidence of OA in this part of the UK. MWFs are an emerging problem, while isocyanates remain the commonest cause. Incidence remained at a fairly stable background level with many small and a few large epidemics superimposed. Schemes like Midland Thoracic Society's Rare Respiratory Disease Registry Surveillance Scheme of Occupational Asthma could help in identifying outbreaks by linking cases at the workplace.

The present study describes salivary cotinine levels and their relationship to cigarettes smoked per day in Mexican smokers. Using a sampling strategy based on the number of cigarettes per day, we recruited 1,222 smokers from Mexico City and the state of Morelos in Mexico during 1999. Smoking behaviors and other factors known to affect nicotine intake and cotinine level were identified in an interview using a standardized questionnaire. Salivary cotinine was measured by capillary gas chromatography with nitrogen-phosphorus detection. We used generalized additive models to describe the relationship between salivary cotinine levels and variables of interest. The mean age of the population was 39.7 years (SD=15.6 years), with a mean cotinine level of 194.7 ng/ml (SD=134.8; range=10.1-767). Participants smoked a mean of 15.5 cigarettes per day (SD=11.3). Salivary cotinine and cigarettes smoked per day were positively related, although the association was not linear, flattening above 20 cigarettes per day. After adjusting for cigarettes per day, we found that significant predictors of cotinine levels included age, body mass index, cigarette producer, and smoking behavior variables. These results may have implications for dosing with nicotine medications to aid smoking cessation in Mexican smokers and suggest that whether the cigarette is labeled light or regular has no relationship to nicotine dose from smoking cigarettes.

SUMMARY Immunoglobulin G (IgG) antibodies against microbes related to indoor dampness problems have been used as potential biomarkers of fungal exposure in clinical investigations. There is limited information on their relation to asthma. We conducted a population-based incident case–control study to assess the risk of asthma in relation to specific IgG antibodies to eight dampness-related microbes: Aspergillus fumigatus, A. versicolor, Cladosporium cladosporioides, Fusarium oxysporum, Sporobolomyces salmonicolor, Stachybotrys chartarum, Streptomyces albus and Trichoderma citrinoviride. We recruited systematically all new cases of asthma during a 2·5-year study period and randomly selected controls from a source population of adults 21–63 years of age living in the Pirkanmaa Hospital District, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls selected randomly from the source population. IgG antibodies were analysed with ELISA. An increased risk of developing asthma in adulthood was significantly related to IgG antibodies to T. citrinoviride, but not to the other moulds. There was no evidence of a dose–response relation between the IgG antibody level and the risk of asthma. T. citrinoviride may play a role in the aetiology of adult-onset asthma or serve as an indicator of other causal factors.

We present the first practical algorithm for the optimal linear leaf ordering of trees that are generated by hierarchical clustering. Hierarchical clustering has been extensively used to analyze gene expression data, and we show how optimal leaf ordering can reveal biological structure that is not observed with an existing heuristic ordering method. For a tree with n leaves, there are 2n−1 linear orderings consistent with the structure of the tree. Our optimal leaf ordering algorithm runs in time O(n4), and we present further improvements that make the running time of our algorithm practical. Contact: {zivbj,gifford}@mit.edu; tommi@ai.mit.edu

The Helsinki Office Environment Study, a population-based cross-sectional study was carried out in Finland in 1991 among 2,678 workers in 41 randomly selected office buildings. The aim was to evaluate the relations between work with office equipment and supplies and the occurrence of eye, nasopharyngeal, skin, and general symptoms (often denoted as sick building syndrome (SBS)), chronic respiratory symptoms, and respiratory infections. Work with self-copying paper was significantly related to weekly work-related eye, nasopharyngeal, and skin symptoms, headache and lethargy, as well as to the occurrence of wheezing, cough, mucus production, sinusitis, and acute bronchitis. Photocopying was related to nasal irritation, and video display terminal work to eye symptoms, headache, and lethargy.

We have studied the expression of prostate-specific antigen (PSA) mRNA by reverse transcriptase-polymerase chain reaction in peripheral blood of 25 patients with cancer of the prostate (CAP), four with benign prostatic hyperplasia (BPH), two with renal stones, three with other types of cancer, and six healthy male and three female controls. Expression of mRNA specific for a certain tissue in peripheral blood is thought to indicate the presence of circulating cancer cells and metastatic spread of a tumor originating from this tissue. We detected PSA mRNA in 9 of 18 CAP patients with metastatic disease but in none of 7 patients without metastases. Negative results in patients with metastatic disease were associated with successful endocrine therapy and low concentrations of serum PSA, and the correlation between serum concentrations of PSA and the presence of PSA mRNA in peripheral blood was statistically significant. PSA mRNA was not found in patients with BPH, other types of cancer, or in healthy controls. Thus the occurrence of PSA mRNA in peripheral blood is associated with metastatic CAP.