Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

BACKGROUND: While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult. OBJECTIVE: A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods. METHODS: In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials. RESULTS: A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 microg of the allergenic food and would continue with doses of 100 microg and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose. CONCLUSION: A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals.

Developmental follow-up in 15-month-old infants of asthmatic vs. control mothers.

The purpose of this study was to evaluate mental and psychomotor development in infants of mothers whose asthma was actively managed during pregnancy and to compare the results with those froms infants of non-asthmatic mothers. Bayley Scales were assessed at age 15 +/- 3 months in 379 infants of asthmatic mothers and 376 control infants. Relationships were assessed between developmental indices and asthma severity, socioeconomic status, and infant prematurity. No significant differences in developmental indices were observed between infants of asthmatic mothers and control infants. No relationships were identified between developmental indices and maternal asthma severity. In the infants of both asthmatic and control mothers, a lower mean psychomotor developmental index was associated with birth weight < 2,500 g, and a lower mental developmental index with lower socioeconomic status. Hence, infants of asthmatic mothers whose asthma has been actively managed during pregnancy have developmental outcomes at 15 months of age that are similar to those of control infants.

Effect of allergist intervention on patient-centered and societal outcomes: allergists as leaders, innovators, and educators.

Atopic disorders, which afflict millions of Americans and hundreds of millions worldwide, are at epidemic levels with concomitant increases in morbidity and mortality. Environmental and lifestyle changes over the past three to five decades are proposed causes for this pandemic and as such present major burdens to reverse. The scope of allergy practice bridges directly on this challenge. Allergy as a specialty is a major leader in developing effective strategies to confront this epidemic. Allergists have made major contributions to the understanding of the risk factors, immunology, pathophysiology, immunomodulation, and prevention of atopic and immunologic disorders. Allergist epidemiologists and clinicians have helped develop and implement national and international guidelines in the recognition, management, and prevention of asthma and rhinitis. Allergist clinical researchers are active in (1) outcomes research that demonstrates convincingly the value of allergy as a specialty in asthma, allergic rhinitis, anaphylaxis, drug and food allergy, and other atopic disorders, (2) National Institutes of Health clinical trials that will form the basis for the future treatment of asthma and allergic disease, and (3) pharmaceutical trials that evaluate new, effective, and safe medication to treat atopic disease. Allergist educators, comprising academic and practicing allergists, supported by allied health professionals, national associations, and affiliated lay organizations, provide comprehensive education to fellows, residents, colleague physicians, media, the public, and patients. Documentation of the value of allergists in improving patient-centered and societal outcomes in their core domain, allergy, is the appropriate final topic contribution in the important series "New millennium: The conquest of allergy."

Relationship between increased airway responsiveness and asthma severity in the childhood asthma management program.

The relationship between increased airway responsiveness and asthma severity in children is unclear. The Childhood Asthma Management Program (CAMP) with 1,041 children with mild to moderate asthma offers an opportunity to relate the concentration of methacholine that causes a 20% fall in FEV(1) (PC(20)) to level of lung function, occurrence of respiratory symptoms, duration of disease, and assessment of severity by clinical staff. Decreasing PC(20) was found to be associated with lower levels of lung function (prebronchodilator percent predicted FEV(1): r = 0.29, beta = 3.5, p < 0.001), the occurrence of chronic asthma symptoms, persistent wheezing (odds ratio [OR] = 1.66, p < 0.001), subjective clinical staff assessment of asthma severity (p < 0.001), and longer duration of asthma (r = -0.11, beta = -0.20, p < 0.002). These data provide evidence that the degree of airway responsiveness is linked to disease severity in children with mild to moderate asthma.

Quantitative IgE antibody assays in allergic diseases.

During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously. Elevated egg-specific IgE antibody levels in infancy are associated with significantly increased risk for development of inhalant allergies later in childhood. In cases of inhalant allergy, specific IgE antibody levels correlate closely with results of inhalation challenge studies in cat-sensitive persons. Also, mite-specific IgE antibody levels correlate significantly with the mite allergen contents of reservoir dust in the homes of mite-sensitive persons. Immunoassays for quantitation of specific IgE antibodies may be used to document allergen sensitization over time and to evaluate the risk of reaction on allergen exposure. However, immunoassays and skin tests are not entirely interchangeable, and neither will replace the other in appropriate circumstances.

Dietary aspects of food allergy prevention in infants and children.

Food allergy occurs in approximately 4% to 6% of children, has increased in prevalence during the past decade, and thus represents a major burden to our young. The natural history of food allergy documents that allergies to cow's milk, egg, and soy frequently remit whereas allergies to peanut, nuts, and fish typically persist to adulthood, although exceptions exist. Food allergen avoidance subsequent to sensitization and manifestation of symptoms appears to hasten tolerance; however, the immunologic mechanism responsible for tolerance to one food group and not another is poorly understood. Identification and characterization of allergens and determination of B- and T-cell epitopes has provided an opportunity to better define these mechanisms. Identifying and developing effective strategies to prevent food and other allergic diseases represents a high priority for medicine at this time because of the unbridled increase in the prevalence and morbidity attributed to them. Immunologic engineering holds the greatest promise for allergy prevention in the not too distant future, but environmental strategies that promote food avoidance provide an avenue for prevention at present. Such efforts rely actively on reducing the food allergenic load and exposure of atopy-prone infants and children.

Soy allergy in infants and children with IgE-associated cow's milk allergy.

OBJECTIVES: To determine the prevalence of soy allergy in IgE-associated cow's milk allergy (CMA). STUDY DESIGN: Children <3.5 years with documented IgE-associated CMA (n = 93) were evaluated for soy allergy by double-blind, placebo-controlled food challenge, open challenge, or convincing previous history of an anaphylactic reaction to soy. Children tolerant to soy at entry received soy formula and were followed up for 1 year. RESULTS: Of this IgE-associated CMA cohort (ages 3 to 41 months), 14% (95% CI = 7. 7%-22.7%) were determined to have soy allergy, 12 definitely at entry and 1 possibly after 1 year of soy ingestion. The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion. Improved growth (P <.05) occurred in the non-soy-allergic cohort ingesting soy formula (579 31 mL/d) during the year of follow-up. CONCLUSIONS: Soy allergy occurs in only a small minority of young children with IgE-associated CMA. As such, soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula.

Relationships between duration of asthma and asthma severity among children in the Childhood Asthma Management Program (CAMP)

BACKGROUND: Many factors, including heredity, atopic status, and environment, have been implicated in the determination of asthma severity. Relatively little is known about the degree to which asthma duration influences asthma severity. OBJECTIVE: The Childhood Asthma Management Program (CAMP), consisting of 1041 children (age 8. 9 +/- 2.1 years at enrollment) with mild-to-moderate asthma, offers an opportunity to examine the relationship between asthma duration and asthma severity. METHODS: By using the extensive CAMP baseline cross-sectional data on asthma duration, spirometry, bronchial responsiveness, symptomatology, and markers of atopy, univariate and multivariate regression models were used to evaluate whether asthma duration is associated with asthma severity. RESULTS: Duration of asthma in the study cohort from time of diagnosis until randomization into CAMP ranged from 0.3 to 12.1 years (mean, 5.0; SD, 2.7; median, 4.8). Asthma duration is associated in univariate analyses both with lower levels of several lung functions (P <.001), including methacholine bronchial reactivity (natural log [ln] FEV1 PC20, mg/mL; r = -0.112), prebronchodilator and postbronchodilator percent predicted FEV1 (r = -0.176 and r = -0.130, respectively), and prebronchodilator and postbronchodilator FEV1 /forced vital capacity (FVC) (%) (r = -0.237 and r = -0.211, respectively), as well as higher levels of symptoms (symptom score: r = 0.147, P <. 001) and borderline greater use of albuterol for symptoms (r = 0.058, P =.064) during a 28-day screening period before randomization. Simple linear regression detected the following differences in lung functions per year of asthma duration: ln FEV1 PC20, -0.050 mg/mL/y; prebronchodilator FEV1, -0.907 percent predicted/y; and prebronchodilator FEV1 /FVC, -0.729 percent predicted/y. After controlling for potential explanatory variables (atopy, inflammatory markers, household Der p 1 levels, anti-inflammatory medication use, and clinical center), regression models revealed that the duration of asthma remained significantly and independently associated with ln FEV1 PC20 (P =.004), prebronchodilator percent predicted FEV1 (P =.043), and prebronchodilator and postbronchodilator FEV1 /FVC (%) (P <.001), as well as being positively associated with mean daily symptom score (P <.001) and albuterol use for symptoms (P =.003) during a 28-day screening period. Duration was also found to be significantly associated with physician/nurse assessment of asthma severity and other historical measures of medication use. CONCLUSIONS: These data demonstrate that asthma duration is associated with lower lung function, greater methacholine responsiveness, more asthma symptomatology, and greater use of as-needed albuterol, which are all measures of asthma severity. As such, early diagnosis and intervention may be necessary to ameliorate these adverse effects of persistent asthma.

Construction and validation of four childhood asthma self-management scales: parent barriers, child and parent self-efficacy, and parent belief in treatment efficacy.

This study examined the psychometric properties of four new health belief measures for asthmatic children and their parents. A total of 110 asthmatic children (aged 7-15) and 129 parents (with asthmatic children aged 3-15) responded to a mail-out survey. Evidence for reliability (0.75-0.87) and validity was obtained for measures of Parent Barriers to Managing Asthma, Parent Asthma Self-Efficacy (subscales: attack prevention and attack management), Parent Treatment Efficacy, and Child Asthma Self-Efficacy (subscales: attack prevention and attack management). All measures were correlated in the hypothesized directions with health status, asthma symptoms, and impact of illness on the family.

Symptoms in pediatric asthmatics and air pollution: differences in effects by symptom severity, anti-inflammatory medication use and particulate averaging time.

Experimental research in humans and animals points to the importance of adverse respiratory effects from short-term particle exposures and to the importance of proinflammatory effects of air pollutants, particularly O(subscript)3. However, particle averaging time has not been subjected to direct scientific evaluation, and there is a lack of epidemiological research examining both this issue and whether modification of air pollutant effects occurs with differences in asthma severity and anti-inflammatory medication use. The present study examined the relationship of adverse asthma symptoms (bothersome or interfered with daily activities or sleep) to O(3) and particles (less than or equal to)10 micrometer (PM10) in a Southern California community in the air inversion zone (1200-2100 ft) with high O(3) and low PM (R = 0.3). A panel of 25 asthmatics 9-17 years of age were followed daily, August through October 1995 (n = 1,759 person-days excluding one subject without symptoms). Exposures included stationary outdoor hourly PM10 (highest 24-hr mean, 54 microgram/m(3), versus median of 1-hr maximums, 56 microgram/m(3) and O(3) (mean of 1-hr maximums, 90 ppb, 5 days (greater than or equal to)120 ppb). Longitudinal regression analyses utilized the generalized estimating equations (GEE) model controlling for autocorrelation, day of week, outdoor fungi, and weather. Asthma symptoms were significantly associated with both outdoor O(3) and PM(10) in single pollutant- and co-regressions, with 1-hr and 8-hr maximum PM(10) having larger effects than the 24-hr mean. Subgroup analyses showed effects of current day PM(10) maximums were strongest in 10 more frequently symptomatic (MS) children: the odds ratios (ORs) for adverse symptoms from 90th percentile increases were 2.24 [95% confidence interval (CI), 1.46-3.46] for 1-hr PM10 (47 microgram/m(3); 1.82 (CI, 1.18-2.81) for 8-hr PM10 (36 microgram/m(3); and 1.50 (CI, 0.80-2.80) for 24-hr PM10 (25 microgram/m(3). Subgroup analyses also showed the effect of current day O(subscript)3 was strongest in 14 less frequently symptomatic (LS) children: the ORs were 2.15 (CI, 1.04-4.44) for 1-hr O(3) (58 ppb) and 1.92 (CI, 0.97-3.80) for 8-hr O(3) (46 ppb). Effects of 24-hr PM10 were seen in both groups, particularly with 5-day moving averages (ORs were 1.95 for MS and 4. 03 for LS; p(less than or equal to)0.05). The largest effects were in 7 LS children not on anti-inflammatory medications [5-day, 8-hr PM10, 9.66 (CI, 2.80-33.21); current day, 1-hr O(3), 4.14 (CI, 1.71-11.85)]. Results suggest that examination of short-term particle excursions, medication use, and symptom severity in longitudinal studies of asthma yields sensitive measures of adverse respiratory effects of air pollution.

Safe administration of influenza vaccine to patients with egg allergy.

OBJECTIVES: Specific recommendations for administering the influenza vaccine to patients with egg allergy are based on limited scientific data. The objectives of this investigation were to determine the safety of a 2-dose administration of an influenza vaccine to patients with egg allergy and to evaluate the usefulness of skin testing with the influenza vaccine before administration. STUDY DESIGN: In this multicenter clinical trial, clinical histories of egg allergy were confirmed by skin testing with egg and, if possible, by oral challenges with egg. Subjects with egg allergy received the vaccine in 2 doses, 30 minutes apart; the first dose was one tenth and the second dose nine tenths of the recommended dose as determined by age. Subjects without egg allergy were recruited as control subjects and received 1 age-determined dose of the vaccine. Skin prick tests with the influenza vaccine were performed on all subjects. RESULTS: From 1994 to 1997, 83 subjects with egg allergy and 124 control subjects were evaluated. The content of ovalbumin/ovomucoid was 0.1, 1.2, and 0.02 micrograms/mL, respectively in the 1994-95, 1995-96, and 1996-97 influenza vaccines. Results of vaccine skin prick tests were positive in 4 subjects with egg allergy and in 1 control subject. All patients with egg allergy tolerated the vaccination protocol without any significant allergic reactions. CONCLUSIONS: These results demonstrate that patients with egg allergy, even those with significant allergic reactions after egg ingestion, can safely receive an influenza vaccine in a 2-dose protocol when the vaccine preparation contains no more than 1.2 micrograms/mL egg protein.

Skin testing with penicilloate and penilloate prepared by an improved method: amoxicillin oral challenge in patients with negative skin test responses to penicillin reagents.

BACKGROUND: Penicillin skin testing has been limited by the lack of commercially available penicilloate and penilloate reagents. OBJECTIVE: This project was proposed to produce a stable, well-characterized supply of penicilloate and penilloate for intrastate use by our health maintenance organization and to document clinical safety and efficacy. METHODS: An improved method of extraction for penicilloate and penilloate, which changed the solvents used during recrystallization, was developed. With these newly prepared reagents, penicillin skin testing was performed on 348 subjects. Skin testing was immediately followed by an oral challenge of 250 mg of amoxicillin in 215 of 288 (75%) subjects displaying a negative response to a battery of penicillin skin tests. RESULTS: Nuclear magnetic resonance and mass spectrometry of the newly produced penicilloate and penilloate showed no evidence of organic contamination. Penicillin skin testing resulted in 17.2% (60 of 348) positive test results, with 20% of the subjects with positive results only responding to the newly produced minor determinants. The rate of mild adverse reactions to penicillin skin testing was 1.1% (4 of 348). The rate of mild acute adverse reactions was 5.1% (11 of 215), and the delayed reaction rate was 0.9% (2 of 215) with the amoxicillin challenge. CONCLUSIONS: This improved penicillin minor determinant extraction method allows for the reproducible production of very pure preparations of penicilloate and penilloate. Large-scale penicillin skin testing, followed by amoxicillin challenge if results are negative is feasible in a large group model health maintenance organization operating within a single state with the use of internally produced penicilloate and penilloate and commercially available penicillin, amoxicillin, and penicilloyl polylysine.

The safety of asthma and allergy medications during pregnancy.

BACKGROUND: Although no asthma or allergy medications can be considered proven safe for use during pregnancy, these medications are often used to prevent the potential direct and indirect consequences of uncontrolled asthma or allergy. OBJECTIVE: The safety of asthma medications, antihistamines, and decongestants was assessed in a prospectively monitored cohort of 824 pregnant women with and 678 pregnant women without asthma. METHODS: Medications used since conception were recorded on each subject's initial visit (< 28 weeks' gestation). Thereafter, diary cards for medications were completed by the patient through the time of delivery. Perinatal outcomes were compared in exposed versus unexposed individuals. A multivariate analysis accounted for the potential effects of age, parity, smoking, race, weight gain during pregnancy, maternal pulmonary function, acute asthmatic episodes, and multiple medication exposure. RESULTS: No significant relationships were identified between major congenital malformations and first trimester or any exposure to beta-agonists, theophylline, cromolyn, corticosteroids, antihistamines, or decongestants. In the multivariate analyses, oral corticosteroids were independently associated with preeclampsia (odds ratio = 2.0, p = 0.027), but no other independent associations were observed between asthma or allergy medications and adverse perinatal outcomes. CONCLUSION: Use of most common asthma and allergy medications during pregnancy was not associated with increased perinatal risks. Maternal use of oral corticosteroids was independently associated with the occurrence of preeclampsia in this study, although the mechanism of this association is not clear. However, because prior observations suggest that severe asthma may be associated with maternal and/or fetal mortality, risk-benefit considerations still favor the use of oral corticosteroids when indicated for the treatment of asthma during pregnancy.

Asthma and allergy in pregnancy.

Rhinitis is extremely common during pregnancy, and asthma is one of the most common potentially serious medical problems to complicate pregnancy. Cutaneous allergy (urticaria/angioedema and eczema) also may occur during pregnancy. All of these entities may worsen with pregnancy in some patients and appear to improve in others. Uncontrolled asthma may directly threaten the fetus, and morbidity from the other illnesses may indirectly affect pregnancy through an effect on eating, sleeping, or emotional well-being. Appropriate diagnosis, avoiding triggering factors when possible; appropriate use of pharmacotherapy; and, when indicated, allergen immunotherapy usually allow these chronic conditions to be controlled during pregnancy so as to optimize both the health of the mother and that of her baby.

The effect of outdoor fungal spore concentrations on daily asthma severity.

The relationship between day-to-day changes in asthma severity and combined exposures to community air pollutants and aeroallergens remains to be clearly defined. We examined the effects of outdoor air pollutants, fungi, and pollen on asthma. Twenty-two asthmatics ages 9-46 years were followed for 8 weeks (9 May-3 July 1994) in a semirural Southern California community around the air inversion base elevation (1,200 ft). Daily diary responses included asthma symptom severity (6 levels), morning and evening peak expiratory flow rates (PEFR), and as-needed beta-agonist inhaler use. Exposures included 24-hr outdoor concentrations of fungi, pollen, and particulate matter with a diameter < 10 microns (PM10; maximum = 51 micrograms/m3) and 12-hour day-time personal ozone (O3) measurements (90th percentile = 38 ppb). Random effects longitudinal regression models controlled for autocorrelation and weather. Higher temperatures were strongly protective, probably due to air conditioning use and diminished indoor allergens during hot, dry periods. Controlling for weather, total fungal spore concentrations were associated with all outcomes: per minimum to 90th percentile increase of nearly 4,000 spores/m3, asthma symptom scores increased 0.36 (95% CI, 0.16-0.56), inhaler use increased 0.33 puffs (95% CI, -0.02-0.69), and evening PEFR decreased 12.1 l/min (95% CI, -1.8-22.3). These associations were greatly enhanced by examining certain fungal types (e.g., Alternaria, basidiospores, and hyphal fragments) and stratifying on 16 asthmatics allergic to tested deuteromycete fungi. There were no significant associations to low levels of pollen or O3, but inhaler use was associated with PM10 (0.15 inhaler puffs/10 micrograms/m3; p < 0.02). These findings suggest that exposure to fungal spores can adversely effect the daily respiratory status of some asthmatics.

Daily asthma severity in relation to personal ozone exposure and outdoor fungal spores.

Epidemiologic investigations of ambient ozone (O3) effects on daily asthma status have not used personal O3 exposures and have often lacked well-characterized allergen exposures. To address this, we studied 12 asthmatic subjects aged 9 to 16 yr, who recorded daily asthma symptoms (functional levels 0 to 5) and as-needed inhaler use during September and October 1993 in San Diego, California, Outdoor aeroallergens, O3, and fine particle concentrations were measured at a central outdoor site, and personal 12-h daytime exposures to O3 were measured daily. Personal O3 differed greatly between subjects and was 27% of mean outdoor O3. In random-effects autoregression models controlling for weekend days and fungal spores, personal O3 was associated with asthma severity: for a 90th percentile increase in O3 (25 ppb), symptom scores increased by 25% (95% CI: 0 to 49%) and inhaler use increased by 26% (95% CI: 3 to 48%) over their averages. Outdoor 12-h O3, but not 1-h maximum O3, was associated with inhaler use (p < 0.03). Fungal spores were significantly associated with symptoms (scores increased by 0.1 to 0.3/1,000 spores/m3) and inhaler use (0.1 to 0.4 puffs/1,000 spores/m3) across speciated groups. Pollen and fine particles (low levels) were not associated with any outcomes. These findings illustrate that the epidemiologic importance of O3 and allergenic cofactors can be underestimated by failure to account for personal O3 and fungal exposures.