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.

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.

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.

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.

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.

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.

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.

Beyond administrative data: characterizing cardiorespiratory disease episodes among patients visiting the emergency department.

We attempted to address deficiencies in administrative health service data during a study of cardiorespiratory emergency department visits. From 1994-1996, we obtained data on 9,264 visits and conducted 1,772 follow-up interviews. The median interval between symptoms and visit ranged from 0.8 days (95% CI 0-1.7) for cardiac conditions to 4.0 days for chronic obstructive pulmonary disease (COPD) (95% CI 2.7-5.3) and respiratory infections (95% CI 3.5-4.5). Infection was the most common trigger of respiratory visits. Although most had improved at follow-up, symptoms persisted following the visit for a mean of 4.5 days (95% CI 3.8-5.4) for cardiac conditions to 8.4 days (95% CI 7.2-9.5) for COPD. Among adults aged < 70, the mean number of reduced activity days per episode ranged from 4.7 (95% CI 3.9-5.4) for asthma to 6.6 (95% CI 5.9-7.4) for respiratory infections. Our data assist in interpreting epidemiological studies based on administrative data, and illustrate the broad impacts of cardiorespiratory disease episodes.

Intubation and mechanical ventilation for COPD: development of an instrument to elicit patient preferences.

BACKGROUND: Whether to simply provide palliative care or to intubate and use mechanical ventilation (MV) in a patient with severe COPD in acute respiratory failure is a difficult decision. The outcome of MV cannot be accurately predicted. Some patients cannot be weaned from the ventilator; those who are weaned often return to chronic severe respiratory disability. It is important that patients participate in this decision, but assistance is required. To address these issues, we developed and pilot-tested an aid to assist patients with MV decisions. METHODS: A scenario-based decision aid was developed consisting of an audiocassette and a booklet describing intubation and MV and its possible outcomes. We used a probability tradeoff technique to elicit the patients' preferences and a decisional conflict scale to evaluate satisfaction. RESULTS: With the assistance of the decision aid, all patients (10 men and 10 women) reached a decision. Two men and all 10 women declined MV. Mean decisional conflict was low (2.2 of a possible 5; SD, 0.9). At 1 year, only two patients (11%) had changed their decision. The agreement between physicians and patients was 65%; between next-of-kin and patients, there was uniform disagreement. CONCLUSION: With the decision aid, stable decisions were made with satisfaction and confidence. Proxy decisions were incongruent, especially when made by family members. The strong gender effect should be further investigated. We suggest that the COPD decision aid be further tested in a community clinical setting.

Residential fungal contamination and health: microbial cohabitants as covariates.

An association between symptoms and residential mold growth has been consistently observed in several countries, but the contribution of dust mites and bacterial endotoxins to this relation has not been established. To address this issue, we studied a sample of 403 Canadian elementary school children during the winter months. Reported mold growth was compared to respiratory and nonspecific symptoms before and after adjusting for dust mite antigens and bacterial endotoxin. A 12-50% relative increase in symptom prevalence was associated with reported mold growth both before and after adjusting for subject characteristics, dust mite antigens, and endotoxins. In conclusion, the association between residential fungal contamination and symptoms is not confounded by dust mites or bacterial endotoxins or other known disease-causing agents.

The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials.

STUDY OBJECTIVE: This study was conducted to determine whether the addition of inhaled ipratropium to inhaled beta-agonist therapy is effective in the treatment of adults with acute asthma exacerbation. METHODS: Published reports of randomized, controlled trials assessing the use of ipratropium and beta-agonists in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, the Cochrane Library, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in English, French, and Italian were identified and assessed for inclusion in the metaanalysis. Randomized, double-blind, placebo-controlled trials were selected in which ipratropium was used as adjunctive therapy to beta-agonists in adult patients with acute asthma exacerbation presenting to a hospital emergency department or similar acute care setting. Data were extracted independently by 2 reviewers. For eligible trials, the mean percent change in peak expiratory flow rate (PEFR), or forced expiratory volume in one second (FEV1), and their SDs were assessed in the ipratropium-treated and control groups. The effect of ipratropium on hospitalization rates and adverse effects were also analyzed. RESULTS: Data from 10 studies, reporting on a total of 1,377 patients with asthma, were pooled using a weighted average method. Compared with placebo, the use of ipratropium was associated with a pooled 7.3% improvement in FEV1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolute improvement in FEV1 in the ipratropium/ beta-agonist group, which was 100 mL (95% CI 50 to 149 mL) above that seen for the group that received beta-agonist without ipratropium. Similarly, the pooled estimate of treatment effect in trials that reported data as PEFR was 22.1% (95% CI 11.0% to 33.2%), corresponding to an absolute peak expiratory flow improvement of 32 L/min (95% CI 16 to 47 L/min) in favor of the ipratropium/ beta-agonist combination group. When these data were combined using effect size as a common measure, the use of ipratropium was associated with a summary effect size of.38 (95% CI.27 to.48). Effect sizes were negatively correlated with baseline mean expiratory flows, suggesting that studies enrolling patients with more severe airflow obstruction showed greater absolute benefits of combination bronchodilator therapy. For the 3 trials reporting hospital admission data (n=1,031), patients receiving ipratropium had a relative risk of hospitalization of .73 (95% CI.53 to .99). The use of ipratropium was not associated with any severe adverse effects when used in conjunction with beta2 -agonists. CONCLUSION: There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive treatment to beta2 -agonists for the treatment of acute asthma exacerbation. Although the clinical significance of this improvement in airflow obstruction remains unclear, it would seem reasonable to recommend the use of combination ipratropium/ beta-agonist therapy in acute adult asthmatic exacerbations, since the addition of ipratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.

How accurate is spirometry at predicting restrictive pulmonary impairment?

OBJECTIVE: To determine the accuracy with which spirometric measurements of FVC and expiratory flow rates can diagnose the presence of a restrictive impairment. DESIGN: The pulmonary function tests of 1,831 consecutive white adult patients who had undergone both spirometry and lung volume measurements on the same visit over a 2-year period were analyzed. The probability of restrictive pulmonary impairment, defined as a reduced total lung capacity (TLC) below the lower limit of the 95% confidence interval, was determined for each of several categoric classifications of the spirometric data, and additionally for each of several interval levels of the FVC and the FEV1/FVC ratio. SETTING: A large clinical laboratory in a university teaching hospital using quality-assured and standardized spirometry and lung volume measurement techniques according to American Thoracic Society standards. RESULTS: Two hundred twenty-five of 1,831 patients (12.3%) had a restrictive defect. The positive predictive value of spirometry for predicting restriction was relatively low; of 470 patients with a low FVC on spirometry, only 41% had restriction confirmed on lung volume measurements. When the analysis was confined to the 264 patients with a restrictive pattern on spirometry (ie, low FVC and normal or above normal FEV1/FVC ratio), the positive predictive value was 58%. Conversely, spirometry had a very favorable negative predictive value; only 2.4% of patients (32 of 1,361) with a normal vital capacity (VC) on spirometry had a restrictive defect by TLC measurement. The probability of a restrictive defect was directly and linearly related to the degree of reduction of FVC when the FVC was < 80% of predicted (p = 6.002). Combining the FVC and the FEV1/FVC ratio improved the predictive ability of spirometry; for all values of FVC < 80% of the predicted amount, the likelihood of restrictive disease increased as the FEV1/FVC ratio increased. CONCLUSIONS: Spirometry is very useful at excluding a restrictive defect. When the VC is within the normal range, the probability of a restrictive defect is < 3%, and unless restrictive lung disease is suspected a priori, measurement of lung volumes can be avoided. However, spirometry is not able to accurately predict lung restriction; < 60% of patients with a classical spirometric restrictive pattern had pulmonary restriction confirmed on lung volume measurements. For these patients, measurement of the TLC is needed to confirm a true restrictive defect.

Testing the association between residential fungus and health using ergosterol measures and cough recordings.

Questionnaire surveys in several countries have consistently detected an association between symptoms and residential mould growth. Confirmation by objective measures would strengthen the argument for causality. To address this issue, quantitative and qualitative fungal measures (airborne ergosterol and viable fungi in dust) were compared to respiratory symptoms (n = 403) and nocturnal cough recordings (n = 145) in Canadian elementary schoolchildren during the winter of 1993-1994. There was a 25 percent to 50 percent relative increase in symptom prevalence when mould was reported to be present (p < 0.05). However, neither symptoms nor recorded cough was related to objective measures of mould. In conclusion, the inability to find an association between objective measures of fungus and health suggest that either these objective measures, or the traditionally used questionnaire data are inaccurate. This discrepancy limits the acceptance of a causal relation between indoor fungal growth and illness.

Management of steroid-dependent asthma with methotrexate: a meta-analysis of randomized clinical trials.

Our objective was to determine whether methotrexate is an effective steroid-sparing agent for patients with severe asthma. Published reports of controlled trials assessing the use of methotrexate in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in any language were identified and assessed for inclusion in the meta-analysis. We selected randomized, double-blind, placebo-controlled trials in which low-dose methotrexate was administered to corticosteroid-dependent asthmatics, and oral steroids were subsequently tapered according to the patients' clinical status. Data were extracted independently by two reviewers. For all eligible trials, the mean reduction in oral corticosteroid dose, the mean change in FEV1, and the standard deviations, were calculated for the treatment and control groups. Data concerning side-effects of therapy were also extracted. Data from 12 studies, reporting on a total of 250 patients, were pooled using a weighted average method, with weights proportional to the inverse of the variance of the treatment effect. Compared to placebo, the use of methotrexate was associated with a pooled 6.0% improvement in FEV1 (95% CI, 1.0-11%) and an 18.2% reduction in oral steroid use (95% CI, 11.7-24.7%). This corresponded to a 3.3 mg day-1 greater reduction in oral steroid use for patients taking methotrexate than for those taking placebo (95% CI, 2.1-4.4 mg day-1). Gastrointestinal complications and transient increases in liver enzymes were more common in patients randomized to methotrexate. Three potentially life-threatening side-effects (two pneumonias and one liver dysfunction) occurred in 159 patients randomized to methotrexate vs. none in those patients on placebo. It was concluded that methotrexate allowed a modest reduction in oral corticosteroid compared to patients receiving placebo. The benefit is relatively small, however, and should be balanced against the potential for side-effects associated with the use of methotrexate.

Superior vena cava obstruction secondary to mediastinal lymphadenopathy in a patient with cystic fibrosis.

Superior vena cava (SVC) obstruction most often is a complication of malignant tumors such as lung cancer or lymphoma. The common use of long-term indwelling central venous catheters also has added to the prevalence of SVC obstruction. This report describes the first case of SVC obstruction in a patient with cystic fibrosis due to extrinsic compression from benign reactive mediastinal lymphadenopathy. Although in these circumstances intravascular thrombosis should be ruled out, extrinsic compression from mediastinal lymphadenopathy should be considered.

The radiographic prevalence of hilar and mediastinal adenopathy in adult cystic fibrosis.

BACKGROUND: It has been stated that the hilar and mediastinal lymph nodes in adults with cystic fibrosis are invariably enlarged from chronic inflammation. However, until correlation with computed tomography and magnetic resonance imaging became possible, the visualization of this feature on plain chest radiographs received very little attention, and even the advent of these modalities, little has been written on the subject. OBJECTIVE AND METHODS: To determine the frequency of positive radiographic evidence of hilar and mediastinal adenopathy, the chest radiographs of 48 adult patients with cystic fibrosis were reviewed. RESULTS: Adenopathy was found in a total of 25 (52%) of the patients hilar in 22 (46%) and mediastinal in 21 (44%). The adenopathy was chronic and slowly progressive in all of the patients, and in no case did it resolve. The distribution of the adenopathy resembled sarcoidosis in 19 of the 25 patients and lymphoma in another patient. CONCLUSIONS: The diagnosis of adenopathy was thought to be acceptably accurate: among patients for whom CT scans were also available, CT confirmed the radiographic diagnosis of abnormality in 22 of 24 sets of hilar lymph nodes and all 14 sets of mediastinal lymph nodes. When observed on chest radiography, mediastinal adenopathy was invariably widespread throughout the mediastinum. The presence of adenopathy was correlated with more severe pulmonary involvement, as assessed by the Brasfield scoring system. However, the importance of observing adenopathy radiographically lies in allaying concerns about the development of sarcoidosis or systemic lymphatic disease in these patients and preventing unnecessary concern and investigation.