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.

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.

Asthma management preceding an emergency department visit.

BACKGROUND: The burden of illness from asthma in North America has not decreased despite advancements in understanding disease pathogenesis and improved pharmacotherapeutics. This study examined the adequacy of preventive measures applied to asthma. METHODS: Using a standardized self-administered questionnaire, 111 consecutive patients presenting to the emergency department because of asthma were surveyed about their "usual" level of disability from asthma, usual medications, self-management plans to deal with an asthma attack, and environmental control measures. RESULTS: Twenty-five percent of subjects suffered sleep disturbance more than 15 days per month, had work/school attendance affected more than 14 days per year, and previously visited an emergency department twice in the past year. Thirty-seven percent had no effective plans to deal with an attack and another 32% had plans that were never discussed with a physician. Although 78% reported that cigarette smoke aggravated their asthma, one third of these were exposed at home. CONCLUSIONS: For a significant proportion of adults requiring emergency health services for asthma, preexisting management was poor by current standards. We recommend that patients be screened by emergency physicians and those with identifiable inadequacies in usual care be referred to physicians with expertise in asthma management.

Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline.

To investigate a possible interaction between norfloxacin and theophylline, eight healthy nonsmoking volunteers (mean age 27 +/- 5.3 years) were administered aminophylline, 5 mg/kg, before and after a 6-day course of norfloxacin, 400 mg every 12 hours, and changes in pharmacokinetic parameters were measured and compared. Norfloxacin induced significant decreases in theophylline clearance (14.9%; p less than 0.01) and the terminal phase slope (13.3%; p less than 0.02) and increased the AUC (16.6%; p less than 0.01). The apparent volume of distribution at steady state was unchanged. The greatest norfloxacin-induced individual change in theophylline clearance was a reduction of 28.6%. Given these findings, we advise that, for patients who are treated with theophylline and are subsequently treated with norfloxacin, adjustment of the theophylline dosage may be necessary in some patients to minimize the risk of theophylline toxicity.

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.

Cancer downwind from sour gas refineries: the perception and the reality of an epidemic.

A rural population in southwestern Alberta, Canada, living downwind from natural gas refineries, has expressed concerns about an excess of adverse health outcomes over the last 25 years. This has escalated to the point of causing a prominent sociopolitical controversy within the province. As part of a large field epidemiologic study undertaken during the summer of 1985 to investigate possible health effects, a residential cohort study was carried out to study cancer incidence. The cohort was defined as all those individuals who resided in the area in 1970. A total of 30,175 person-years of risk within Alberta were experienced by this cohort from 1970 to 1984. The incident cancers during this period were enumerated by computerized record linkage with the Alberta Cancer Registry. Age- and sex-standardized incidence ratios, based on expected rates from three prespecified demographically similar, nonmetropolitan Southern Alberta populations, were 1.05, 1.09, and 1.03, respectively, none of which was significantly different from unity. Although they do not address the issue of etiologic association, these data can provide considerable reassurance to a community that was convinced it had experienced an epidemic of cancer.

Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.

OBJECTIVE: To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. METHODS: 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. RESULTS: Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05). CONCLUSION: In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

Quality-of-life following thoracotomy for lung cancer.

Contrary to the issues of perioperative morbidity and survival following surgery for lung cancer, little attention has been given to quality-of-life. To address this, quality-of-life was assessed preoperatively and 1, 3, 6 and 9 months postoperatively in a cohort of 117 consecutive subjects who underwent thoracotomy with a certain or presumptive diagnosis of lung cancer. Those with cancer (n = 91) confirmed at thoracotomy were contrasted to those without (n = 26). Moderate to severe dyspnea, reported in 14% preoperatively, increased to 34% at 1 and 3 months (p < 0.005) but returned to approximately 10% at 6 and 9 months. Similarly, activities of daily living were impaired in 11% preoperatively; this disability increased to 21% at 1 month (p < 0.005), and returned to baseline at 6 and 9 months. Those with cancer compared to those without a postoperative diagnosis of cancer had similar quality-of-life preoperatively but deteriorated more in the postoperative period. This study demonstrates that important deterioration in quality-of-life occurs during the first 3 months postoperatively in those with a final diagnosis of cancer but improvement back to baseline can be expected thereafter.

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.

Clinical prediction of airways hyperresponsiveness.

We tested the ability of chest physicians to detect increased airways responsiveness (IAR) in patients presenting with symptoms suggestive of asthma. Physicians ordering bronchial provocation tests for diagnostic purposes were asked to predict the clinical probability (based on the patient's history, examination, and spirometry) of IAR (defined by a PC20 for FEV1 less than or equal to 8 mg/ml of histamine). Presenting symptoms in the 38 subjects aged 16 to 78 years included cough, wheeze, dyspnea, chest tightness, and recurrent colds. There was no association between IAR and clinical probability dichotomized as less than or equal to 50 percent or greater than 50 percent (p = .16, Fisher test). The association was no stronger using only subjects in whom the clinical prediction was greater than 67 percent or less than 33 percent. If knowledge of the level of airway reactivity would influence subsequent patient management (eg, prescription of antiasthmatic therapy), then its clinical prediction should not be relied upon.

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.

Severe exacerbations of COPD and asthma. Incremental benefit of adding ipratropium to usual therapy.

Single dose studies have assessed the utility of ipratropium bromide alone or with beta agonists in the short- and long-term management of chronic obstructive lung disease and asthma. We performed a randomized, double-blind trial to assess the incremental benefit over 24 hours of adding ipratropium vs placebo to a standardized regimen of medications commonly used in the acute and subsequent hospital management of COPD and asthma. Sixty-eight subjects received nebulized salbutamol, intravenous methylprednisolone, intravenous aminophylline, and antibiotics and were randomized to receive either 80 micrograms of ipratropium or placebo via metered dose inhaler and spacing device with each salbutamol treatment (6 to 8 times per day). Among the 50 patients who completed the study, there were no significant differences between ipratropium and placebo groups with respect to baseline FEV1, FVC, and PaCO2. The improvement of FEV1 from baseline to 24 hours was 294 (SD = 568) ml in the ipratropium group vs 393 (SD = 622) ml in placebo group. Adjusting FEV1 by age, gender, and smoking did not significantly alter the findings. Those with an admission diagnosis of asthma showed larger 24 hour FEV1 responses (487 ml in ipratropium vs 801 ml in placebo) than those with COPD (149 ml ipratropium vs 102 ml in placebo). However, within these two strata, there were no significant differences in FEV1 improvement between ipratropium and placebo groups. This study suggests that if ipratropium is used in the initial emergency treatment of COPD or asthma, it could safely be discontinued by 24 hours in order to reduce the cost and complexity of therapy.

Preoperative prediction of pulmonary complications following thoracic surgery.

The ability of preoperative quality-of-life and physiologic variables to predict postoperative complications was tested in 117 consecutive patients undergoing thoracotomy for possible or definite lung cancer. Preoperatively, quality of life was globally assessed by the QLI and Sickness Impact Profile. Dyspnea was assessed by the Clinical Dyspnea Index and a modified Pneumoconiosis Research Unit question. Spirometry and maximal exercise testing were carried out in 115 and 46 subjects, respectively. Thirty-seven percent experienced at least one respiratory complication (eg, pneumonia, atelectasis prompting bronchoscopy, pulmonary embolism). Twofold or greater increases in respiratory complications were associated with current smoking (p < 0.05), cancer as the final pathologic condition (p < 0.10), at least moderate dyspnea (p < 0.10), FEV 1 < 60 percent of predicted (p < 0.05), ventilatory reserve < 25 L (p < 0.05), and VO2max < 1.25 L (p < 0.05). Twofold increases in the incidence of any complication (respiratory, cardiac, etc) were associated with age > or = 75 years (p < 0.05) and cancer as the final pathologic condition (p < 0.05). We conclude that simple historic information (age, smoking status, cancer status, dyspnea) indicates the risk of postoperative morbidity. General quality-of-life measures were not good predictors of morbidity. Our findings corroborate the few studies supporting the value of VO2max and suggest that the usefulness of the ventilatory reserve deserves further attention.

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.

Indoor air quality and health: validity and determinants of reported home dampness and moulds.

BACKGROUND: Questionnaire-based surveys from several countries have consistently detected adverse health associated with home dampness and mould growth. METHODS: To test the validity of questions commonly used to indicate the presence of indoor mould, questionnaires were administered in 403 homes where dust samples were taken for viable fungi and air samples for ergosterol. RESULTS: Geometric mean concentrations of the total viable fungi were 255 (SE 116) x 10(3) CFU/g when mouldy odours were reported and 155 (SE 55) when odours were not reported (P = 0.01). Similarly, reported water damage was associated with a 50% increase (P = 0.06). Geometric mean concentrations of the predominantly indoor-source fungi, Aspergillus plus Penicillium, were twice as high when mould or mildew was reported than when not mentioned (P = 0.01). The presence of reported mould or water damage was unrelated to the presence of detectable levels of ergosterol. There was evidence for reporting bias: in the presence of low concentrations of viable fungi in dust, respondents reporting allergies were more likely to report visible mould growth (odds ratio [OR] = 1.8, 95% confidence interval [CI]: 0.9-3.5, P = 0.10. In the presence of elevated concentrations of dust fungi, respondents who smoked were less likely to report visible mould growth, (OR = 0.4, 95% CI: 0.2-0.7, P = 0.005). CONCLUSIONS: Reported mould, water damage, and mouldy odours were associated with elevated levels of indoor fungi. However, inaccuracy was high and there was evidence of a systematic reporting bias. Future research should concentrate on developing accurate objective measures of exposure to fungi, and then use this information to develop valid questionnaires. Currently, objective measures not questionnaires, are recommended to clarify the health effects of indoor fungi.

Prevalence of childhood asthma across Canada.

BACKGROUND: A large cross-sectional study provided an opportunity to estimate the prevalence of childhood asthma in several regions across Canada. METHODS: In 1988, approximately 18,000 questionnaires were distributed to the families of 5-8 year old children in 30 communities from the following six regions across Canada: the interior of British Columbia, southeastern Saskatchewan, southwestern Ontario, the central region of Ontario, southern Quebec, and the Maritimes (Nova Scotia and Prince Edward Island). These communities were free of point-source air pollutants and selected to represent a range of ambient sulphate concentrations. In all 14,948 questionnaires were returned representing an 83% response rate. RESULTS: Currently present, physician-diagnosed asthma was reported for 4.7% of children by their parents. Persistent wheezing was reported for 13% and persistent cough for 5.9%. Asthma was most common in the two Maritime provinces (7.4%), and least common in British Columbia (3.3%) and Quebec (3.4%). Similar regional differences were seen for persistent cough, persistent wheeze, and also hospital separation rates for asthma which were approximately 800 per 100,000 for the Maritimes and 396 per 100,000 for British Columbia. Differences persisted despite adjustments for several host and environmental (indoor and outdoor) characteristics. CONCLUSIONS: The east coast of Canada may be an endemic area of asthma in Canada. If confirmed by objective measures of asthma, a detailed aetiologic investigation could enhance understanding of this phenomenon and the major environmental determinants of asthma morbidity in general.

Cystic fibrosis carrier screening in a high-risk population. Participation based on a traditional recruitment process.

OBJECTIVE: Recent advances in molecular genetic (DNA) technology have permitted identification of previously undetectable cystic fibrosis (CF) carriers. Although research has been initiated in the general population, to our knowledge no published studies have looked at the utilization of DNA-based carrier screening in the high-risk CF population (family history of CF). DESIGN: Cross-sectional, diagnostic open trial. SETTING: Carrier testing was offered to a high-risk CF population via adult patients with CF or parents of pediatric patients with CF attending two regional CF clinics over a 3-year period. PARTICIPANTS: Consecutive sample of virtually all patients with CF (n = 118) from a population of 1 million. MAIN RESULTS: Despite free services, written follow-up, and counseling for 99% of patients attending the CF clinic, there was less than 10% participation from high-risk family members (168 blood relatives and 26 spouses of identified carriers or patients with CF; 38 and 156 persons from the adult and pediatric clinic families, respectively). Nevertheless, we identified 91 CF carriers among the 168 high-risk relatives. This is comparable to the number of carriers detected in general population carrier screening that has tested substantially more individuals (> 3000 per study). CONCLUSIONS: Our results suggest that research concerning CF carrier screening not only focus on data about fundamental program resources and numbers of carriers detected but also investigate how information about the availability of carrier screening is disseminated, the motivation behind testing, and the perceived relevance of test results by those tested in the high-risk population. These issues are increasingly relevant as screening becomes feasible using DNA testing for far more prevalent disorders (such as breast cancer and diabetes).

Chronic cough responsive to ibuprofen.

A 57-year-old woman believed that ibuprofen, prescribed for back pain, improved her idiopathic chronic cough that had been resistant to inhaled and oral corticosteroids. To confirm this observation, we performed an n-of-1 clinical trial with four treatment periods, each separated by a 4-day washout. Ibuprofen 1800 mg/day for 6 days or placebo was randomly allocated in a double-blind fashion with a block size of 4. The number of coughs during the first 30 minutes after awakening were counted daily throughout the study using a tape recorder. Sixty-two coughs/hour occurred while taking ibuprofen, compared with 164 with placebo. We conclude that ibuprofen may be effective in idiopathic chronic cough, and suggest that prostaglandins may be pathogenic factors in some patients.

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.

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.