Physical characterization of a low-charge glycoform of the MUC5B mucin comprising the gel-phase of an asthmatic respiratory mucous plug.
We have previously noted that sequential extraction of an asthmatic mucous exudate with 6 M guanidinium chloride yielded a fraction of the mucins that were most resistant to solubilization and of high Mr [Sheehan, Richardson, Fung, Howard and Thornton (1995) Am. J. Respir. Cell Mol. Biol. 13, 748-756]. Here we show that this mucin fraction is dominated (at least 96% of the total) by the low-charge glycoform of the MUC5B gene product. Seen in the electron microscope the mucins appeared mainly as compact 'island' structures composed of linear threads often emanating from globular 'nodes' rather than the discrete linear threads more typical of mucins that we have previously described. The effect of reducing agents was as expected for other gel-forming mucins, i.e. reduced subunits or monomers of Mr 3x10(6)) were produced within 15 min of treatment. Kinetic experiments on the cleavage of the intact mucins with the proteinase trypsin indicated two clear regimes of fragmentation. An initial rapid cleavage generated mucins ranging from Mr=4x10(6) to 30x10(6) that in the electron microscope appeared as polydisperse threads (500-3000 nm in length), similar to normal and other respiratory mucins that we have previously characterized. A subsequent slower fragmentation over many hours yielded a major fragment of Mr 3x10(6) and length 200-600 nm, very similar in size and Mr to the subunits obtained by reduction. The results suggest that the MUC5B mucin is assembled, first into polydisperse linear threads, which are then linked together via a protein-mediated process. This might involve part of the mucin polypeptide or an as yet unidentified protein(s). The high proteinase susceptibility of the linkage suggests that it might be a point of control for mucin size and thus mucus rheology. (+info)
Respiratory symptoms among glass bottle workers--cough and airways irritancy syndrome?
Glass bottle workers have been shown to experience an excess of respiratory symptoms. This work describes in detail the symptoms reported by a cohort of 69 symptomatic glass bottle workers. Symptoms, employment history and clinical investigations including radiology, spirometry and serial peak expiratory flow rate records were retrospectively analyzed from clinical records. The results showed a consistent syndrome of work-related eye, nose and throat irritation followed after a variable period by shortness of breath. The latent interval between starting work and first developing symptoms was typically 4 years (median = 4 yrs; range = 0-28). The interval preceding the development of dysponea was longer and much more variable (median = 16 yrs; range = 3-40). Spirometry was not markedly abnormal in the group but 57% of workers had abnormal serial peak expiratory flow rate charts. Workers in this industry experience upper and lower respiratory tract symptoms consistent with irritant exposure. The long-term functional significance of these symptoms should be formally investigated. (+info)
Asthma visits to emergency rooms and soybean unloading in the harbors of Valencia and A Coruna, Spain.
Soybean unloading in the harbor of Barcelona, Spain, has been associated with large increases in the numbers of asthma patients treated in emergency departments between 1981 and 1987. In this study, the association between asthma and soybean unloading in two other Spanish cities, Valencia and A Coruna, was assessed. Asthma admissions were retrospectively identified for the period 1993-1995, and harbor activities were investigated in each location. Two approaches were used to assess the association between asthma and soybean unloading: One used unusual asthma days (days with an unusually high number of emergency room asthma visits) as an effect measure, and the other estimated the relative increase in the daily number of emergency room visits by autoregressive Poisson regression, adjusted for meteorologic variables, seasonality, and influenza incidence. No association between unusual asthma days and soya unloading was observed in either Valencia or A Coruna, except for one particular dock in Valencia. When the association between unloaded products and the daily number of emergency asthma visits was studied, a statistically significant association was observed for unloading of soya husk (relative risk = 1.50, 95% confidence interval 1.16-1.94) and soybeans (relative risk = 1.31, 95% confidence interval 1.08-1.59) in A Coruna. In Valencia, a statistical association was found only for the unloading of soybeans at two particular docks. Although these findings support the notion that asthma outbreaks are not a common hidden condition in most harbors where soybeans are unloaded, the weak associations reported are likely to be causal. Therefore, appropriate control measures should be implemented to avoid soybean dust emissions, particularly in harbors with populations living in the vicinity. (+info)
Beta2-adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting beta2-agonist therapy.
The aim of the present study was to investigate bronchoprotective sensitivity in patients receiving regular treatment with short- and long-acting beta2-agonists and to evaluate any possible association with genetic polymorphism. Thirty-eight patients with stable mild to moderate asthma and receiving inhaled corticosteroids were randomized in a parallel group, double-blind, double-dummy fashion to receive 2 weeks of treatment with either formoterol (12 microg once daily, 6 microg twice daily or 24 microg twice daily) or terbutaline (500 microg four times daily). Bronchoprotection against methacholine challenge (as a provocative dose to produce a 20% fall in forced expiratory volume in 1.0 s: PD20) was measured at baseline (unprotected) after an initial 1 week run-in without beta2-agonist, and at 1 h after the first and last doses of each treatment. The PD20 values were log-transformed and calculated as change from baseline. Percentage desensitization of log PD20 for first- versus last-dose bronchoprotection was calculated and analysed according to effects of treatment and beta2-adrenoceptor polymorphism at codon 16 or 27. The mean degree of desensitization for bronchoprotection was comparable with all four treatments and there were no significant differences in absolute PD20 values after 2 weeks of chronic dosing. The PD20 values were (as microg of methacholine, geometric means+/-S. E.M.): formoterol, 12 microg once daily, 99+/-42 microg; formoterol, 6 microg twice daily, 107+/-44 microg; formoterol, 24 microg twice daily, 108+/-45 microg; terbutaline, 500 microg four times daily, 88+/-37 microg. All patients receiving formoterol, 24 microg twice daily, exhibited a loss of protection greater than 30% which was unrelated to polymorphism at codon 16 or 27. For codon 16, the use of lower doses of formoterol (12 microg once daily or 6 microg twice daily) showed wider variability in the propensity for protection loss in patients who were heterozygous, in contrast to a more uniform protection loss seen with homozygous glycine patients. The amount of protection loss was not significantly related to polymorphism at codon 16 or 27, expressed as values (mean+/-S.E.M.) for percentage desensitization according to each genotype (pooled treatments): Gly-16, 66+/-11%; Het-16, 53+/-8%; Arg-16, 69+/-18%; Glu-27, 68+/-12%; Het-27, 58+/-8%; Gln-27, 52+/-12%. The results of this preliminary study showed that bronchoprotective desensitization occurred readily in response to short- or long-acting beta2-agonist exposure irrespective of beta2-adrenoceptor polymorphism at codon 16 or 27. Further studies with larger patient numbers are required to further evaluate the effects of polymorphisms with lower doses of regular formoterol. (+info)
Management of asthma and COPD patients: feasibility of the application of guidelines in general practice.
OBJECTIVE: To examine the feasibility of the application of guidelines to the management of asthma and chronic obstructive pulmonary disease (COPD) by assessing compliance with the guidelines and listing the barriers general practitioners (GPs) encountered during implementation. Insight into the feasibility of individual items in the guidelines can guide implementation strategies in the future and, if necessary, support revision of the guidelines. DESIGN: Descriptive study of care delivered during the implementation of guidelines by means of documentation of the care provided, education, feedback on compliance and peer review. SETTING: General practice. STUDY PARTICIPANTS: Sixteen GPs in 14 general practices. MAIN OUTCOME MEASURES: Compliance was expressed as the percentage of patients per practice managed by the GPs according to the guidelines. For each patient (n=413) data were collected on the care delivered during the first year of the implementation. Barriers encountered were derived from the summaries of the discussions held during the monthly meetings. RESULTS: The GPs were most compliant on the items 'PEFR measurement at every consultation' (98%), 'allergy test' (78%) and 'advice to stop smoking' (82%), and less compliant on the items 'four or more consultations a year' (46%), 'ordering spirometry' (33%), 'adjustment of medication' (42%), 'check on inhalation technique' (38%) and referral to a chest physician (17%) or a district nurse (5%). The main barriers were the amount of time to be invested, doubts about the necessity of regular consultations and about the indications for ordering spirometry and for referral to a chest physician or a district nurse. CONCLUSION: Although the feasibility was assessed in a fairly optimal situation, compliance with the guidelines was not maximal, and differed between the individual items of care. Suggestions are given for further improvements in compliance with the guidelines and for revision of the guidelines. (+info)
Elevated asthma morbidity in Puerto Rican children: a review of possible risk and prognostic factors.
Latino children represent a significant proportion of all US children, and asthma is the most common chronic illness affecting them. Previous research has revealed surprising differences in health among Latino children with asthma of varying countries of family origin. For instance, Puerto Rican children have a higher prevalence of asthma than Mexican American or Cuban American children. In addition, there are important differences in family structure and socioeconomic status among these Latino populations: Cuban Americans have higher levels of education and family income than Mexican-Americans and Puerto Ricans; mainland Puerto Rican children have the highest proportion of households led by a single mother. Our review of past research documents differences in asthma outcomes among Latino children and identifies the possible genetic, environmental, and health care factors associated with these differences. Based on this review, we propose research studies designed to differentiate between mutable and immutable risk and prognostic factors. We also propose that the sociocultural milieus of Latino subgroups of different ethnic and geographic origin are associated with varying patterns of risk factors that in turn lead to different morbidity patterns. Our analysis provides a blue-print for future research, policy development, and the evaluation of multifactorial interventions involving the collaboration of multiple social sectors, such as health care, public health, education, and public and private agencies. (+info)
Cockroach allergy and asthma in a 30-year-old man.
A growing body of evidence has implicated allergens derived from cockroaches as an important environmental factor that may aggravate asthma in sensitized persons. We present the case of a 30-year-old man with asthma and a cockroach allergy. Allergy skin testing confirmed hypersensitivity to cockroach extract, and a home visit revealed visual evidence of infestation and the presence of Bla g 1 German cockroach allergen in vacuumed dust. As is typical of patients with a cockroach allergy and asthma, multiple factors in addition to cockroach allergen appeared to aggravate the patient's asthma. A multimodality therapeutic regimen, which included medications as well as cleaning of the home, integrated pest management, and professional application of chemical controls, resulted in substantial clinical improvement. The pathophysiology, epidemiology, and clinical features of cockroach-allergic asthma are reviewed, and an approach to diagnosis and management is suggested. (+info)
Short-term associations between outdoor air pollution and visits to accident and emergency departments in London for respiratory complaints.
Many epidemiological studies have shown positive short-term associations between health and current levels of outdoor air pollution. The aim of this study was to investigate the association between air pollution and the number of visits to accident and emergency (A&E) departments in London for respiratory complaints. A&E visits include the less severe cases of acute respiratory disease and are unrestricted by bed availability. Daily counts of visits to 12 London A&E departments for asthma, other respiratory complaints, and both combined for a number of age groups were constructed from manual registers of visits for the period 1992-1994. A Poisson regression allowing for seasonal patterns, meteorological conditions and influenza epidemics was used to assess the associations between the number of visits and six pollutants: nitrogen dioxide, ozone, sulphur dioxide, carbon monoxide, and particles measured as black smoke (BS) and particles with a median aerodynamic diameter of <10 microm (PM10). After making an allowance for the multiplicity of tests, there remained strong associations between visits for all respiratory complaints and increases in SO2: a 2.8% (95% confidence interval (CI) 0.7-4.9) increase in the number of visits for a 18 microg x (-3) increase (10th-90th percentile range) and a 3.0% (95% CI 0.8-5.2) increase for a 31 microg x m(-3) increase in PM10. There were also significant associations between visits for asthma and SO2, NO2 and PM10. No significant associations between O3 and any of the respiratory complaints investigated were found. Because of the strong correlation between pollutants, it was difficult to identify a single pollutant responsible for the associations found in the analyses. This study suggests that the levels of air pollution currently experienced in London are linked to short-term increases in the number of people visiting accident and emergency departments with respiratory complaints. (+info)