Air pollution and hospitalization for venous thromboembolic disease in Chile.

BACKGROUND: Ambient air pollution is a risk factor for stroke and myocardial infarction, possibly because of alterations in coagulation that influence the arterial circulation. Whether air pollution influences diseases associated with peripheral venous thrombogenesis remains largely unknown. OBJECTIVES: To determine the association between air pollution and venous thromboembolic disease (VTE) in a sample of the general population. METHODS: A time-series analysis was used to test the association between daily air pollution and VTE hospitalizations in Santiago between 2001 and 2005. Results were adjusted for long-term trends, day of the week and average daily humidex. RESULTS: From a population of 5.4 million, there were, on average, 2.3 admissions for VTE per day. Pooled estimates of relative risk (RR) [95% confidence interval (CI)] of hospitalization for venous disease were: 1.07 (1.05, 1.09) for a 58.4 p.p.b. increase in ozone (O(3)); 1.06 (1.02, 1.09) for a 5.85 p.p.b. increase in sulphur dioxide (SO(2)); 1.08 (1.03, 1.12) for a 29.25 microg/m(3) increase in nitrogen dioxide (NO(2)); and 1.05 (1.03, 1.06) for a 20.02 microg/m(3) increase in particulate matter < or = 2.5 microm in mean aerodynamic diameter (PM(2.5)). For pulmonary embolism (PE) results were: 1.10 (1.07, 1.13) for O(3); 1.05 (1.02, 1.08) for SO(2); 1.07 (1.04, 1.09) for NO(2); and 1.05(1.03, 1.06) for PM(2.5), respectively. CONCLUSION: Air pollution appears to be a risk factor for venous thrombosis and PE, a disease with a significant fatality rate.

Heat recovery ventilators prevent respiratory disorders in Inuit children.

UNLABELLED: Inuit infants have high rates of reported hospitalization for respiratory infection, associated with overcrowding and reduced ventilation. We performed a randomized, double-blind, placebo controlled trial to determine whether home heat recovery ventilators (HRV) would improve ventilation and reduce the risk of respiratory illnesses in young Inuit children. Inuit children under 6 years of age living in several communities in Nunavut, Canada were randomized to receive an active or placebo HRV. We monitored respiratory symptoms, health center encounters, and indoor air quality for 6 months. HRVs were placed in 68 homes, and 51 houses could be analyzed. Subjects had a mean age of 26.8 months. Active HRVs brought indoor carbon dioxide concentrations to within recommended concentrations. Relative humidity was also reduced. Use of HRV, compared with placebo, was associated with a progressive fall in the odds ratio for reported wheeze of 12.3% per week (95%CI 1.9-21.6%, P = 0.022). Rates of reported rhinitis were significantly lower in the HRV group than the placebo group in month 1 (odds ratio 0.20, 95%CI 0.058-0.69, P = 0.011) and in month 4 (odds ratio 0.24, 95%CI 0.054-0.90, P = 0.035). There were no significant reductions in the number of health center encounters, and there were no hospitalizations. Use of HRVs was associated with in improvement in air quality and reductions in reported respiratory symptoms in Inuit children. PRACTICAL IMPLICATIONS: Reduced ventilation is common in the houses of Inuit children in arctic Canada, and is associated with an increased risk of respiratory infection. Installation of HRV brings indoor carbon dioxide concentration, as a marker of adequate ventilation, to within recommended concentrations, although relative humidity is also reduced. Installation of HRV is associated with improvements in indoor air quality, and a reduced risk of wheezing and rhinitis not associated with cold air exposure in young Inuit children. Further research is required to explore traditional Inuit cultural attitudes about air movement in dwellings.

Acute effects of outdoor air pollution on forced expiratory volume in 1 s: a panel study of schoolchildren with asthma.

Urban air pollution has been associated with morbidity but little information exists on how it affects diurnal variation of lung function in children with asthma. The purpose of this study was to investigate the acute effects of traffic-related pollution on lung function among children with asthma. We recorded morning and evening forced expiratory volume in 1 s (FEV(1)) for 28 consecutive days in 182 elementary schoolchildren with physician-diagnosed asthma, and monitored ambient hourly air pollution concentrations. An interquartile range (IQR) increase (6.0 microg m(-3)) in the previous 24-h (20:00 h to 20:00 h) mean concentration of fine particulate matter 2.5 microm in diameter (PM(2.5)) was associated with a 0.54% (95% confidence interval (CI) 0.06-1.02) decrease in bedtime FEV(1) (p = 0.027). This association persisted in two-pollutant models with ozone, nitrogen dioxide and sulphur dioxide. An IQR increase in mean daytime (08:00 h to 20:00 h) PM(2.5) of 6.5 microg m(-3) was associated with a 0.73% (95% CI 0.10-1.37) decrease in FEV(1) over the course of the day expressed as 100 x (FEV(1) bedtime - FEV(1) morning)/FEV(1) morning (p = 0.024). This study suggests that, in children with asthma, relatively low concentrations of urban air pollution worsen lung function over a short period of time, even within a day. Of the pollutants measured, PM(2.5 )appears to be the most important.

Sex differences in the clinical presentation and management of airflow obstruction.

The aim of the present study was to explore differences in the clinical expression, clinical diagnoses and management of airway diseases in a primary-care setting. Patients aged >or=35 yrs who had ever smoked were enrolled when they presented for any reason to one of eight rural primary-care practices. Respiratory symptom questionnaires and spirometry were administered. In total, 1,034 patients had acceptable and reproducible spirometry, of whom 550 (53%) were males and 484 (47%) were females. Males smoked more than females (41.2 versus 29.2 pack-yrs) respectively, and were more likely to have a pre-bronchodilator forced expiratory volume in one second/forced vital capacity <0.70 at 22.4 versus 11.8%, respectively. However, more females than males reported breathlessness (51.0 versus 42.8%, respectively), a prior diagnosis compatible with airflow obstruction and taking respiratory medications (23.4 versus 14.9%, respectively). In conclusion, the current results suggest that females are more likely than males to report breathlessness and be prescribed respiratory medications independent of differences in the severity of airflow obstruction.

Treating asthma with omega-3 fatty acids: where is the evidence? A systematic review.

BACKGROUND: Considerable interest exists in the potential therapeutic value of dietary supplementation with the omega-3 fatty acids. Given the interplay between pro-inflammatory omega-6 fatty acids, and the less pro-inflammatory omega-3 fatty acids, it has been thought that the latter could play a key role in treating or preventing asthma. The purpose was to systematically review the scientific-medical literature in order to identify, appraise, and synthesize the evidence for possible treatment effects of omega-3 fatty acids in asthma. METHODS: Medline, Premedline, Embase, Cochrane Central Register of Controlled Trials, CAB Health, and, Dissertation Abstracts were searched to April 2003. We included randomized controlled trials (RCT's) of subjects of any age that used any foods or extracts containing omega-3 fatty acids as treatment or prevention for asthma. Data included all asthma related outcomes, potential covariates, characteristics of the study, design, population, intervention/exposure, comparators, and co interventions. RESULTS: Ten RCT's were found pertinent to the present report. CONCLUSION: Given the largely inconsistent picture within and across respiratory outcomes, it is impossible to determine whether or not omega-3 fatty acids are an efficacious adjuvant or monotherapy for children or adults. Based on this systematic review we recommend a large randomized controlled study of the effects of high-dose encapsulated omega-3 fatty acids on ventilatory and inflammatory measures of asthma controlling diet and other asthma risk factors. This review was limited because Meta-analysis was considered inappropriate due to missing data; poorly or heterogeneously defined populations, interventions, intervention-comparator combinations, and outcomes. In addition, small sample sizes made it impossible to meaningfully assess the impact on clinical outcomes of co-variables. Last, few significant effects were found.

Indoor air quality risk factors for severe lower respiratory tract infections in Inuit infants in Baffin Region, Nunavut: a pilot study.

Inuit infants have extremely high rates of lower respiratory tract infection (LRTI), but the causes for this are unclear. The aims of this study were to assess, in young Inuit children in Baffin Region, Nunavut, the feasibility of an epidemiologic study of the association between indoor air quality (IAQ) and respiratory health; to obtain data on IAQ in their housing; and to identify and classify risk factors for LRTI. Twenty houses in Cape Dorset, Nunavut with children below 2 years of age, were evaluated using a structured housing inspection and measurement of IAQ parameters, and a respiratory health questionnaire was administered. Twenty-five percent of the children had, at some time, been hospitalized for chest illness. Houses were very small, and had a median of six occupants per house. Forty-one percent of the houses had a calculated natural air change rate <0.35 air changes per hour. NO(2) concentrations were within the acceptable range. Smokers were present in at least 90% of the households, and nicotine concentrations exceeded 1.5 microg/m(3) in 25% of the dwellings. Particulates were found to be correlated closely with nicotine but not with NO(2) concentrations, suggesting that their main source was cigarette smoking rather than leakage from furnaces. Mattress fungal levels were markedly increased, although building fungal concentrations were low. Dust-mites were virtually non-existent. Potential risk factors related to IAQ for viral LRTI in Inuit infants were observed in this study, including reduced air exchange and environmental tobacco smoke exposure. Severe lower respiratory tract infection is common in Inuit infants. We found reduced air change rates and high occupancy levels in houses in Cape Dorset, which may increase the risk of respiratory infections. This suggests the measures to promote better ventilation or more housing may be beneficial. Further health benefits may be obtained by reducing bed sharing by infants and greater turnover of mattresses, which were found to have high levels of fungi.

Is outdoor air pollution associated with physician visits for allergic rhinitis among the elderly in Toronto, Canada?

BACKGROUND: While a number of studies suggest that air pollution is associated with allergic rhinitis in children, findings among adults have been equivocal. The aim of this study was to examine the relationship between outdoor air pollution and physician visits for allergic rhinitis among individuals>or=65 years of age in Toronto, Canada. METHODS: Physician visits were identified by using data from the Ontario provincial health insurance plan that is made available to all residents. Our analyses are based on 52,691 physician visits for allergic rhinitis among individuals>or=65 years of age in the Toronto metropolitan area between 1995 and 2000. Generalized linear models were used to regress daily counts of physician visits against daily measures of gaseous and particulate components of air pollution after controlling for seasonality, potential confounders (temperature, relative humidity, aeroallergens), overdispersion and serial correlation. RESULTS: A large number of comparisons were undertaken, with most showing no statistically significant associations between daily levels of air pollution and the number of physician visits for rhinitis. In contrast, an interquartile increase in the 10-day average of ragweed particles increased the mean number of daily rhinitis consultations by 6.4% (95% CI=0.7-12.4%). CONCLUSIONS: Our findings suggest that outdoor air pollution is a poor predictor of physician visits for allergic rhinitis among the elderly.

A comparison of airborne ergosterol, glucan and Air-O-Cell data in relation to physical assessments of mold damage and some other parameters.

UNLABELLED: We report here a comparison of long duration air samples in 110 homes where the material collected on open faced filter cassettes was analyzed for beta 1,3-d glucan, ergosterol, cholesterol and endotoxin. These data were then compared to careful estimates of visible mold and Air-O-Cell data. All the values found except cholesterol were of a similar magnitude to values reported in the limited number of studies available. Glucan was measured with a factor G based assay of the Limulus Amebocyte Lysate followed by size exclusion chromatography. This showed that the majority of airborne glucan found in these houses was fungal in origin arising from both yeasts and intact spores, as well as hyphal and spore fragments. Hyphal and spore fragments together represented 16% of the intact spore counts but over a broad range. Correlations between airborne glucan were strong for ergosterol and visible mold. However, airborne ergosterol was more highly correlated to visible mold than glucan. Endotoxin and Air-O-Cell measurements were poorly or not related to the other measures in the study. This study provides confidence that long duration air samples of the toxin glucan and ergosterol are related to building damage. PRACTICAL IMPLICATIONS: Some studies of damp buildings have shown a relationship between extent of water/mold damage and symptoms. This study compared long duration air samples for glucan and ergosterol to extent of visible mold in houses measuring also the nature of the glucans present. Both measures were highly correlated to extent of visible mold damage in the houses; ergosterol was somewhat superior. Spore counts or prevalence of Asp/Pen in Air-O-Cell samples was not related to extent of visible mold damage but the observation of hyphal fragments was more likely when mold damage was present. This indicates that rigorous assessment of mold damage is a useful measure.

Sex-related interactive effect of smoking and household pets on asthma incidence.

The authors examined the interactive effect of smoking and pets at home on the incidence of asthma and the difference between sexes. The longitudinal data from the first two cycles of the National Population Health Survey, conducted in Canada, were used. A total of 12,636 subjects who reported no asthma at baseline were included in the analysis. The 2-yr cumulative incidence of asthma was higher in females than in males. Female sex and household pets demonstrated a significant interaction in the development of asthma. After adjustment for age, immigration and history of allergy, the odds ratio for smoking in relation to the asthma incidence was 2.50 (95% confidence interval: 1.24-5.05) for females who had pets at home and close to unity for those who had no pets. The incidence of asthma was not associated with smoking status and household pets in males. These results indicate that smoking, having pets at home and other environmental factors can partly explain asthma morbidity among female Canadians.

Influence of family income on hospital visits for asthma among Canadian school children.

BACKGROUND: A study was undertaken to investigate the mechanisms by which socioeconomic status may influence asthma morbidity in Canada. METHODS: A total of 2968 schoolchildren aged 5-19 years with reported asthma were divided into three family income ranges. Hospital visits and risk factors for asthma, ascertained by questionnaire, were compared between the three groups. RESULTS: The mean (SE) annual period prevalence of a hospital visit was 25.0 (3.1)% among schoolchildren with household incomes of less than $20 000 Canadian compared with 16.0 (1.3)% among those with incomes of more than $60 000 (p<0.05). Students with asthma from lower income households were more likely to be younger and exposed to environmental tobacco smoke and cats, and their parents were more likely to have a lower educational attainment and be unmarried (p<0.05). Across all income groups, younger age, lower parental education, having unmarried parents, and regular exposure to environmental tobacco smoke were each associated with an increase in risk of a hospital visit (p<0.05). No increased risk was detected due to sex, having pets, and not taking dust control measures. Although not statistically significant at p<0.05, there may have been an interactive effect between income and susceptibility to environmental tobacco smoke. In the lower income group those children who were regularly exposed to second hand smoke had a 79% higher risk of a hospital visit compared with a 45% higher risk in the higher income group. In a logistic regression model the association between income and hospital visit was no longer significant after adjusting for differences in reported exposure to passive smoking. CONCLUSION: Socially disadvantaged Canadian schoolchildren have increased asthma morbidity. Exposure to cigarette smoke appears to be one important explanation for this observation.

Asthma and the risk of hospitalization in Canada : the role of socioeconomic and demographic factors.

OBJECTIVE: Asthma is an important determinant of hospitalization. The study aims to examine the modifying effects of demographic and socioeconomic factors on the relationship between asthma and the overall number of hospitalizations. METHODS: We examined the data on 17,601 Canadians who were > or = 12 years of age to explore the combined effects of asthma and other factors on hospitalization within the context of a publicly funded health-care system. Asthma was determined by an affirmative response to the question: "Do you have asthma diagnosed by a health professional?" The subjects also were asked whether they had been an overnight patient in a hospital during the past 12 months. RESULTS: Asthma as a risk factor explained 3.7% of all hospitalizations of men and 2.4% of all hospitalizations of women. Overall, hospitalization was positively associated with female gender, old age, and low household income. The odds ratio for asthma as a risk factor for overall hospitalization (ie, hospitalization for any reason and all causes, not only for asthma) was greater for younger men than for older men, for less-educated women than for well-educated women, and for men with middle or high incomes than for men with low incomes. CONCLUSIONS: These results suggest that demographic and socioeconomic factors play a role in the relationship between asthma and the overall number of hospitalizations, with certain population subgroups being at greater risk of hospitalization in relation to asthma.

Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease.

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation in the airways and lung parenchyma; however, little is known about the inflammatory response during acute COPD exacerbation. The objectives of this study were (1) to determine if inflammatory markers associated with neutrophilic inflammation and activation increase at times of acute COPD exacerbation relative to the clinically stable state, and (2) to determine whether the presence of acute bacterial or viral infection at the time of COPD exacerbation could be correlated with increases in sputum markers of inflammation. Induced sputum was collected from patients with COPD when they were clinically stable, during the time of an acute exacerbation, and 1 mo later. Sputum was analyzed at each time point for soluble markers associated with neutrophilic inflammation; myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8). Serologic assays on acute and convalescent sera were performed for respiratory viruses, and induced sputum was also subject to quantitative bacterial cultures, viral cultures, and polymerase chain reaction (PCR) for detection of respiratory viruses. Fourteen of the 50 patients enrolled in the study met predetermined criteria for an acute COPD exacerbation over the 15-mo study period. TNF-alpha and IL-8 were significantly elevated in the sputum of patients during acute COPD exacerbation compared with when they were clinically stable (p = 0.01 and p = 0.05, respectively). Concentrations of these cytokines declined significantly 1 mo after the exacerbation. Three of 14 patients (21%) had confirmed bacterial or viral respiratory tract infections. Patients with documented infection did not demonstrate greater increases in sputum levels of inflammatory cytokines during exacerbations compared with patients without demonstrable infection. We conclude that markers of airway neutrophilic inflammation increase at the time of acute COPD exacerbation and then decline 1 mo later, and that this acute inflammatory response appears to occur independently of a demonstrable viral or bacterial airway infection.

Leisure-time energy expenditure in asthmatics and non-asthmatics.

An association between obesity and asthma has been documented previously, but the nature of this relationship remains unknown. This study aimed to determine if asthma is associated with a sedentary lifestyle which may explain this association. The energy expenditure (EE) on leisure activities was examined in 16,813 subjects, of at least 12 years of age, who participated in the Canadian National Population Health Survey 1994-95. Energy expenditure was calculated by multiplying the duration of leisure-time physical activity by its estimated metabolic energy cost. Asthma was considered to be present if an affirmative response was given to the question, 'Do you have asthma diagnosed by a health professional?' The average EE (+/- standard error) in males was 2.47 (+/- 0.11) kcal kg(-1) day(-1) for asthmatics and 1.98 (+/- 0.03) kcal kg(-1) day(-1) for non-asthmatics. The corresponding average EEs in females were 1.77 (+/- 0.08) and 1.54 (+/- 0.02) kcal kg(-1) day(-1) for asthmatics and non-asthmatics, respectively. The mean EE values decreased with increasing age. A significant interaction between asthma and age was noted with respect to EE; asthmatics tended to have higher mean EE values than non-asthmatics among younger subjects, and lower mean EE values in older subjects. This effect was more pronounced in females than in males. It was concluded that asthmatics were not consistently inactive compared with non-asthmatics. Leisure-time physical activity cannot explain the positive association between obesity and asthma.

Association between ozone and hospitalization for acute respiratory diseases in children less than 2 years of age.

To clarify the health effects of ozone exposure in young children, the authors studied the association between air pollution and hospital admissions for acute respiratory problems in children less than 2 years of age during the 15-year period from 1980 to 1994 in Toronto, Canada. The daily time series of admissions was adjusted for the influences of day of the week, season, and weather. A 35% (95% confidence interval: 19%, 52%) increase in the daily hospitalization rate for respiratory problems was associated with a 5-day moving average of the daily 1-hour maximum ozone concentration of 45 parts per billion, the May-August average value. The ozone effect persisted after adjustment for other ambient air pollutants or weather variables. Ozone was not associated with hospital admissions during the September-April period. Ambient ozone levels in the summertime should be considered a risk factor for respiratory problems in children less than 2 years of age.

Influence of ambient fungal spores on emergency visits for asthma to a regional children's hospital.

The impact of ambient aeroallergens on morbidity from childhood asthma is largely unknown. To address this issue, we studied the association between daily emergency department visits for asthma to a children's hospital, and daily concentrations of both pollen grains and fungal spores during a 5-yr period between 1993 and 1997. Air pollution and meteorological data accounted for in the analyses included ozone, nitrogen dioxide, sulfur dioxide, sulfates, temperature, barometric pressure, and relative humidity. The daily number of asthma visits ranged from 0 to 36 per day with an average of 7.5. Fungal spores, but not pollen grains, were associated with visits (p < 0.05). The percentage increase associated with each group, independent of the others, was 1.9% (SE 0.9) for deuteromycetes, 4.1% (1.6) for basidiomycetes, 2.8% (1.0) for ascomycetes, and 8.8% for these spores combined. In summary, fungal spores account for a significant proportion of the asthma exacerbations in children that prompt an emergency department visit.

Restriction site mapping of the mitochondrial DNA of the four-wing flyingfish, Hirundichthys affinis.

Mitochondrial DNA was isolated from samples of the four-wing flyingfish, Hirundichthys affinis, collected in Barbados in January 1996 and subjected to restriction enzyme analysis, using 13 restriction endonucleases which recognise hexanucleotide sequences, in single and double digests. The resulting restricted DNA fragments were used to map the 14 enzyme recognition sites of 6 endonucleases (7 had no sites) on the flyingfish mtDNA molecule for the first time. In addition, the mtDNA D-loop region was positioned on the restriction site map, for the first time, by selective restriction digestion of the mtDNA molecule followed by polymerase chain reaction (PCR) amplification of the resulting fragments using specific mtDNA D-loop primers. The size of the flyingfish mtDNA molecule (18 kb) was also determined.

Air pollution, aeroallergens and cardiorespiratory emergency department visits in Saint John, Canada.

Existing studies of the association between air pollution, aeroallergens and emergency department (ED) visits have generally examined the effects of a few pollutants or aeroallergens on individual conditions such as asthma or chronic obstructive pulmonary disease. In this study, we considered a wide variety of respiratory and cardiac conditions and an extensive set of pollutants and aeroallergens, and utilized prospectively collected information on possible effect modifiers which would not normally be available from purely administrative data. The association between air pollution, aeroallergens and cardiorespiratory ED visits (n = 19,821) was examined for the period 1992 to 1996 using generalized additive models. ED visit, air pollution and aeroallergen time series were prefiltered using LOESS smoothers to minimize temporal confounding, and a parsimonious model was constructed to control for confounding by weather and day of week. Multipollutant and multi-aeroallergen models were constructed using stepwise procedures and sensitivity analyses were conducted by season, diagnosis, and selected individual characteristics or effect modifiers. In single-pollutant models, positive effects of all pollutants but NO2 and COH were observed on asthma visits, and positive effects on all respiratory diagnosis groups were observed for O3, SO2, PM10, PM2.5, and SO4(2-). Among cardiac conditions, only dysrhythmia visits were positively associated with all measures of particulate matter. In the final year-round multipollutant models, a 20.9% increase in cardiac ED visits was attributed to the combination of O3 (16.0%, 95% CI 2.8-30.9) and SO2 (4.9%, 95%CI 1.7-8.2) at the mean concentration of each pollutant. In the final multipollutant model for respiratory visits, O3 accounted for 3.9% of visits (95% CI 0.8-7.2), and SO2 for 3.7% (95% CI 1.5-6.0), whereas a weak, negative association was observed with NO2. In multi-aeroallergen models of warm season asthma ED visits, Ascomycetes, Alternaria and small round fungal spores accounted for 4.5% (95% CI 1.8-7.4), 4.7% (95% CI 1.0-8.6) and 3.0% (95% CI 0.8-5.1), respectively, of visits at their mean concentrations, and these effects were not sensitive to adjustment for air pollution effects. In conclusion, we observed a significant influence of the air pollution mix on cardiac and respiratory ED visits. Although in single-pollutant models, positive associations were noted between ED visits and some measures of particulate matter, in multipollutant models, pollutant gases, particularly ozone, exhibited more consistent effects. Aeroallergens were also significantly associated with warm season asthma ED visits.

The costs of cardiorespiratory disease episodes in a study of emergency department use.

OBJECTIVE: The average per person direct cost of illness of cardiorespiratory disease episodes was estimated based on a prospective study of emergency department visits. METHODS: Economic modelling of health care costs using prospectively collected resource utilization data (9/1/94 to 8/31/95) from hospital emergency department visitors assigned a diagnosis of asthma, chronic obstructive pulmonary disease (COPD), respiratory infections or cardiac conditions. RESULTS: The total direct costs (1997 CDN$) [95% C.I.] per patient were $1,043.55 [$922.65, $1,164.47] for asthma, $1,690.11 [$1,276.92, $2,103.30] for COPD, $676.50 [$574.46, $778.54] for respiratory infections, and $3,318.74 [$2,937.72, $3,699.76] for cardiac conditions. CONCLUSIONS: This study showed that on average, patients diagnosed with a cardiac condition had the highest total direct cost. Hospitalization cost was the largest component of costs for all diagnoses except asthma, for which medications were the single largest component of direct costs.