Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children

Article Outline

• Abstract
• Methods
• Results
• Discussion
• References
• Copyright

Background

Although sensitization to fungal allergens is prevalent in inner-city children with asthma, the relationship between fungal exposure and morbidity is poorly understood.

Objective

We examined relationships between fungal sensitization, exposure, and asthma morbidity in inner-city children.

Methods

Participants were 5 to 11 years old and enrolled in the Inner-City Asthma Study. This report includes the subset of children with at least 1 positive skin test (PST) response to a fungal allergen extract; for these children, indoor and outdoor airborne culturable fungi levels were measured at baseline and throughout the 2-year study. Asthma morbidity measures were collected prospectively. The primary outcome was symptom days per 2 weeks.

Results

At baseline, children with a PST response to a fungal allergen extract had significantly more symptom days compared with those without a PST response to any fungal allergen extract (6.3 vs 5.7 days per 2 weeks, P = .04). During the study, increases in total fungal exposure and indoor Penicillium species exposure were associated with increases in symptom days and asthma-related unscheduled visits. Indoor exposures to total fungi and to Penicillium species were associated with significant increases in unscheduled visits, even after controlling for outdoor fungal levels. Adverse effects associated with exposure to a specific fungus were stronger among children with PST responses to that fungal allergen extract compared with those seen in children with negative skin test responses.

Conclusion

Outdoor fungal exposure is primarily associated with increased asthma symptoms and increased risk of exacerbations in this population.

Key words: Asthma, inner city, airborne fungi, indoor fungi, outdoor fungi, fungal allergens, children

Abbreviations used: DG18, Dichloran glycerol agar, ICAS, Inner-City Asthma Study, MSD, Maximum symptom day, NHLBI, National Heart, Lung, and Blood Institute, NST, Negative skin test, OR, Odds ratio, PST, Positive skin test, UV, Unscheduled visit

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Sensitization to fungal allergens is prevalent in inner-city children with asthma.¹ Although the contributions of allergens, such as cockroach, dust mite, and mouse, have been explored in this population, relatively few studies have focused on relationships between fungal allergen sensitization, exposure, and morbidity. Those reports have found conflicting results. An Institute of Medicine report concluded that although there is evidence of an association between indoor fungi and asthma symptoms in sensitized individuals, there is insufficient evidence of a causal relationship.² Their conclusions are mainly based on studies of self-reported visual mold or dampness rather than measured fungi. Indeed, the relationship between fungal exposure and asthma morbidity remains poorly understood. Cross-sectional studies demonstrate associations between exposure to high concentrations of indoor fungi³, ⁴, ⁵, ⁶, ⁷, ⁸ and the presence of asthma or asthma-related measures, such as symptoms or medication use, whereas others⁹, ¹⁰, ¹¹, ¹², ¹³, ¹⁴ have not. Several reports indicate that outdoor fungal exposure is associated with asthma exacerbations,¹⁵ pulmonary function,¹⁶ and medication use,¹⁷ but others⁴, ⁹, ¹⁸ have not. A 4-year prospective study of inner-city children found that allergen sensitization did not contribute to the seasonal increase in asthma that occurs in the fall (when outdoor fungal concentrations peak) and postulated that another seasonal factor, viral infection, might account for such variation.¹⁹

Given inner-city housing conditions, such as poor ventilation, leaks, and other factors¹, ²⁰, ²¹ that might potentiate problems related to indoor allergens, fungi could be particularly important determinants of asthma morbidity for children living in these areas. Because asthma morbidity is disproportionately increased in inner-city children, further investigation of the role of fungi is warranted. Although previous work from the Inner-City Asthma Study (ICAS) assessed home fungal exposure, this study investigates the health effects of fungal exposure in those children sensitized to fungal allergens who participated in the ICAS. Primary outcomes included symptoms and exacerbations, measures of impairment, and risk, as outlined in the National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines.²²

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Methods 

The ICAS was a multicenter, randomized controlled trial of environmental intervention to reduce asthma morbidity in which 937 inner-city children aged 5 to 11 years with moderate-to-severe asthma were enrolled. This analysis includes all ICAS participants with a positive skin test (PST) response to at least 1 fungal allergen extract (n = 469). All caregivers provided written informed consent. Details regarding recruitment methods, eligibility criteria, and baseline clinical information for participants have been previously published.¹ Indoor and outdoor airborne culturable fungi levels were measured for those children with at least 1 PST response to a fungal allergen extract. The study protocol was approved by the institutional review boards at the participating centers.

Trained staff administered a baseline interview to the primary caretaker. Subsequent asthma morbidity was measured at 2-month intervals over 2 years by telephone. The primary outcome, maximum symptom days (MSDs) per 2 weeks,¹, ²³, ²⁴, ²⁵ was the largest value among (1) number of days in the past 2 weeks that the child experienced wheezing, chest tightness, or cough; (2) number of nights that the child awoke because of asthma; and (3) number of days that the child had to slow down or discontinue play because of asthma. In addition, the caretaker reported the number of schooldays missed because of asthma, caretaker days of lost sleep within the last 2 weeks, hospitalizations, scheduled and unscheduled clinic visits caused by asthma, and emergency department visits for asthma within the last 2 months. Total asthma-related unscheduled visits (UVs) represented the sum of unscheduled clinic visits and emergency department visits.

During the baseline evaluation, children underwent skin testing (MultiTest II; Lincoln Diagnostics, Decatur, Ill) to histamine and saline controls and 11 allergens, including 4 fungal allergen extracts: Alternaria alternata, 1:20 wt/vol; Cladosporium herbarum, 1:40 wt/vol; Penicillium chrysogenum, 1:20 wt/vol; Aspergillus species mix, 1:20 wt/vol (A flavus, A fumigatus, A glaucus, A nidulans, and A niger); Dermatophagoides farinae; Dermatophagoides pteronyssinus; cockroach mix (German and American); rat; mouse; cat (standardized 10,000 BAU/mL); and dog (mixed breeds). Extracts were ordered from Greer Laboratories (Lenoir, NC), except for cockroach mix (Bayer Corp, Spokane, Wash). A wheal diameter at least 2 mm larger than that elicited by the negative control was considered positive.

Staff performed home evaluations¹ 1 to 3 weeks after the baseline evaluation and every 6 months for 2 years, for a total of 5 assessments. Indoor and outdoor air samples for fungi were both obtained during each home visit by using a single-stage Burkard Portable Culture Plate Air Sampler (Burkard Manufacturing Co, Rickmansworth, United Kingdom) loaded with a dichloran glycerol agar (DG18)–filled Petri dish (Remel Laboratories, Lenexa, Kan). The sampling method, which had a well-established precedent, was chosen for its relative ease of analysis.²⁶ DG18 was used because it enables the growth and enumeration of many xerophilic fungi commonly present in homes while not significantly affecting other fungi.²⁶ Bacterial growth was minimized through the use of DG18. The collection time for each sample was 60 seconds (average air volume sampled, 30.5 L). Two consecutive samples were collected outside the participant's home near the main door. If the outdoor temperature was 36°F (2.2°C) or less, outdoor sampling was not performed. Two consecutive samples were collected in the center of the child's bedroom approximately 1 m above the floor. Culture plates were shipped on the day of collection for overnight delivery to a central laboratory. Culture plates were incubated at room temperature (mean, 40 days), and colonies were identified to the genus level, where possible. Results were reported as colony-forming units per cubic meter of air. The methods relating to air-sampling techniques and fungal analyses used in the ICAS have been published elsewhere.²¹

By using a standardized protocol and equipment, separate vacuumed dust samples were collected from the child's bedroom floor and bed. Samples were separated, sealed, and shipped to a central laboratory for allergen measurement (Der p 1, Der f 1, Bla g 1, Fel d 1, Can f 1, and Mus m 1) by means of ELISA with accepted protocols.²⁷, ²⁸, ²⁹

We used a positive-hole correction³⁰ to correct for the finite number of impaction sites on the plate. (A limited number of impaction sites could adversely affect the number of spores that could be collected.) This positive-hole correction scales total positive colony counts to an estimate of the number of colonies that would have been observed with unlimited impaction sites. Count data were subsequently converted to colony-forming units per cubic meter of air by dividing the corrected colony count by the volume of air sampled.

Single indoor and outdoor values were computed as the mean of the 2 consecutive indoor and outdoor plate values (colony-forming units per cubic meter of air). Correlations between indoor and outdoor concentrations of airborne fungi were analyzed after log₁₀ transformation (after addition of a small constant in light of 0 values) because of highly skewed distributions.

Each 6-month sample was linked to the nearest morbidity follow-up telephone calls surrounding the sample collection date; that is, calls at 4, 6, and 8 months were tied to the 6-month sample. Generalized linear mixed-effect models were fit to predict MSDs and any UVs for asthma. For the analyses, fungi were classified as follows: (1) specific fungus represented an individual genus; (2) the 4 most common fungi combined represented the sum of Alternaria, Aspergillus, Cladosporium, and Penicillium species; and (3) total fungi represented the sum of all detectable fungi. For each outcome and type of fungus, 3 separate models were fit: indoor fungal concentration as the morbidity predictor, outdoor concentration as the predictor, and indoor concentration controlling for outdoor concentration. For the last model, both were entered as covariates in the model predicting symptoms; however, we report the effects of indoor concentration and treat outdoor concentration as a nuisance variable. Other fixed effects included environmental intervention group, site, month of the year, bed dust mite allergen levels, and floor cockroach and cat allergen levels. Subject intercepts were included as random effects. For MSDs, a normal distribution with an identity link was used; for any UVs, a binomial distribution with logit link was used, and thus the estimates returned for those outcomes are odds ratios (ORs).

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Results 

Nine hundred thirty-six children completed the original ICAS intervention study. Fifty percent (n = 469) of children had a PST response to at least 1 fungal allergen extract.¹, ²¹ These children are included in the present study. Alternaria species sensitization was most prevalent (36%).²⁴ Sensitization to Aspergillus, Cladosporium, and Penicillium species was found in 27%, 18%, and 13% of children, respectively.²⁴ Indoor and outdoor air sampling were performed in 469 households. Of 4690 possible samples that could have been obtained, 3759 were collected (1799 outdoor and 1960 indoor samples). Characteristics of all ICAS participants, comparing children with negative skin test (NST) responses to any fungal allergen extract with children with PST responses to any fungal allergen extract (those who are included in this study), are presented in Table I. At baseline, children with PST responses to a fungal allergen had significantly higher asthma morbidity compared with children with NST responses to fungal allergens, as reflected by mean MSDs (6.3 vs 5.7 per 2 weeks, P = .04). Children with PST responses to a fungal allergen extract were sensitized to more indoor allergens. After adjusting for degree of atopy (defined by total number of PST responses to indoor allergens), we found that degree of atopy did not change the baseline relationship between sensitization to fungal allergens and asthma morbidity. There were no differences between groups in other baseline variables, including exposure to various indoor allergens.

Table I. Baseline characteristics∗

Table II presents baseline correlations between various fungi. Correlations were seen between levels of Cladosporium and Alternaria species both indoors (0.46) and outdoors (0.49). Weaker correlations were seen between indoor (0.33) and outdoor (0.30) concentrations of Penicillium and Aspergillus species and outdoor concentrations of Penicillium and Cladosporium species (0.31).

Table II. Baseline fungal correlations (Pearson correlation and 95% CI)

Site	Alternaria species	Cladosporium species	Aspergillus species	Penicillium species
Indoor
Alternaria species	1.00	0.46 (0.38 to 0.53)	−0.02 (−0.11 to 0.08)	0.03 (−0.06 to 0.12)
Cladosporium species		1.00	−0.04 (−0.13 to 0.05)	0.19 (0.10 to 0.28)
Aspergillus species			1.00	0.33 (0.24 to 0.41)
Penicillium species				1.00
Outdoor
Alternaria species	1.00	0.49 (0.41 to 0.56)	0.20 (0.10 to 0.29)	0.03 (−0.07 to 0.13)
Cladosporium species		1.00	0.11 (0.01 to 0.20)	0.31 (0.22 to 0.39)
Aspergillus species			1.00	0.30 (0.21 to 0.39)
Penicillium species				1.00

More than 15 genera of fungi were measurable in inner-city homes, but Cladosporium, Penicillium, Aspergillus, and Alternaria species were the most commonly detected.²¹ For the present study, we first looked at total detectable fungi and subsequently focused on the 4 most commonly detected genera. For children sensitized to fungal allergens, the effects of outdoor and indoor fungal exposure on asthma symptoms are presented in Table III. For each 10-fold increase in outdoor exposure to total fungi, there was a statistically significant increase of 1.39 MSDs per 2 weeks (P < .01). These findings persisted for outdoor exposure to the combined count of the 4 most common fungi (1.33 days per 2 weeks, P < .01). For each 10-fold increase in indoor exposure to total fungi and the 4 most common fungi combined, similar effects on MSDs were seen (1.43 days and 1.32 days per 2 weeks, P < .01 for both). After controlling for outdoor exposure, effects of indoor total fungi on MSDs were reduced in magnitude and no longer significant.

Table III. Health effects associated with 10-fold increase∗ in concentration of fungi among subjects with PST responses to fungal allergen extract

Similar analyses were performed for the 4 genera separately. For each 10-fold increase in outdoor exposure, there was a statistically significant effect, with an excess of 1.28 MSDs over 2 weeks for Alternaria species (P < .01), 1.34 MSDs for Aspergillus species (P = .01), 1.25 MSDs for Cladosporium species (P < .01), and 1.42 MSDs for Penicillium species (P < .01). Similar effects were seen for indoor exposure to the individual genera, but these were no longer significant after controlling for outdoor exposure, except for Penicillium species (1.19 MSDs per 2 weeks, P = .03).

The relative importance of outdoor versus indoor fungi differed when we analyzed the effect of fungal exposure on asthma exacerbations requiring UVs. As shown in Table III, outdoor fungal exposure had no effect on UVs in the prior 2 months for total fungi, the 4 most common fungi combined, or individual genera, except for Aspergillus species (OR, 1.18; 95% CI, 1.01-1.37). In contrast, indoor total fungal exposure was associated with UVs; for each 10-fold increase in total indoor fungi concentration, we found a statistically significant effect (OR, 1.16; 95% CI, 1.02-1.33). For indoor exposure to each of the 4 most common fungi, only Penicillium species demonstrated an effect on UVs (OR, 1.13; 95% CI, 1.04-1.24). After adjusting for outdoor fungal exposure, the associations for indoor total fungi and Penicillium species on UVs persisted, and the effect of the 4 most common fungi combined became significant (OR, 1.13; 95% CI, 1.01-1.26).

We examined the health effects associated with exposure to a particular fungal genus among those children who had an NST response to that particular fungal allergen extract. (These children had PST responses to ≥1 of the other fungal allergen extracts.) As shown in Table IV, outdoor exposure to Alternaria species was associated with health effects among those with NST response to Alternaria species. For each 10-fold increase in outdoor Alternaria species exposure, Alternaria species–nonsensitized children (who were sensitized to ≥1 other fungal allergen extracts) experienced an excess of 1.32 MSDs per 2 weeks (P < .01). We found similarly significant relationships between increasing Penicillium species exposure and MSDs (1.27 days per 2 weeks, P < .01) among children with NST responses to Penicillium species. Indoors, only Penicillium species demonstrated a significant effect on MSDs (1.22 days per 2 weeks, P < .01). After controlling for outdoor exposure, we found no effect of indoor exposure to any fungus, including Penicillium species, among Penicillium species–nonsensitized children.

Table IV. Health effects associated with 10-fold increase∗ in concentration of fungi among children with NST responses to a particular fungal allergen extract

When we examined UVs, only indoor Penicillium species exposure demonstrated an effect for Penicillium species–nonsensitized children (OR, 1.11; 95% CI, 1.03-1.20). This finding persisted after controlling for outdoor exposure.

Comparing Table III, Table IV, the associations of outdoor and indoor fungal concentrations with symptoms were stronger for specific fungi among subjects with PST responses to fungi as opposed to those with NST responses.

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Discussion 

This report presents the respiratory health effects of airborne fungi in a sample of atopic inner-city children with moderate-to-severe asthma. Children sensitized to fungal allergens had increased asthma impairment, as defined by the NHLBI asthma guidelines,²² reflected by more symptom days compared with those seen in children with NST responses to fungal allergen extracts. These associations did not change after adjusting for degree of atopy (ie, number of PST responses to indoor allergens). These findings might reflect a distinct effect of fungal allergen sensitization on asthma morbidity and impairment. Outdoor fungal exposure was more strongly related to symptom impairment, whereas indoor exposure appeared to increase exacerbations (as measured based on UVs), an indicator of risk per the NHLBI guidelines.²² During the prospective 2-year study, variability in outdoor exposure to total fungi, including the 4 most commonly recovered genera (Alternaria, Aspergillus, Cladosporium, and Penicillium species), was significantly associated with changes in asthma related symptom days. Although we found only a modest increased risk of UVs caused by exposure to fungal spores, such exposure might account for considerable morbidity in this population given the high proportion of children sensitized to fungi. Our findings are consistent with those of Delfino et al.¹⁷ In contrast, a study of inner-city Chicago children found no association between frequency of asthma symptoms and outdoor levels of fungi, which were measured at a single location in the city.⁴ Atopic status was not assessed in the Chicago study, whereas our population consisted only of children sensitized to fungal allergens.

Individual variations in outdoor exposure to Aspergillus, Cladosporium, and Penicillium species were associated with significant effects on asthma morbidity. These effects were stronger among those who were sensitized and exposed to the individual fungus examined versus those who were sensitized to other fungal allergens, although health effects were observed in this group as well. We did not observe similar effects for Alternaria species. A prior publication showed a relationship between Alternaria species sensitization, asthma severity, and risk¹⁵ but did not establish an effect of the fungus itself. A cross-sectional study of US homes found indoor Alternaria species levels were associated with asthma medication use but not wheezing.³ Allergy skin tests were not performed in that study. It is possible that low variability and relatively low concentrations of Alternaria species might explain the lack of effect in our study. Alternaria species is a relatively large spore that might not penetrate indoor environments as easily as other fungi. Alternatively, these spores might not remain airborne as long as smaller-spored fungi, especially in relatively still indoor air, so that Alternaria species exposure might not have been effectively estimated by using the air-sampling methodology (short-term samples during a period of minimal disturbance) used. Spores might not be a reliable measure of allergen because allergen expression varies over fungal lifecycles and under different environmental conditions.³¹, ³² After controlling for outdoor exposure, we found that indoor Penicillium species uniquely affected both symptoms and UVs. Similarly, an association between asthma symptoms and bedroom Penicillium species levels was demonstrated in another urban study.⁴ We hypothesize that the differential effects of outdoor versus indoor fungal exposure on symptoms and exacerbations might be related to intensity of exposure; that is, indoor exposure might constitute a more intense exposure of greater duration in a relatively damp, musty, or poorly ventilated environment, as described in inner-city homes,¹, ²¹ compared with outdoor exposure, which typically occurs for brief periods, thus causing less severe symptoms. However, given the brief collection period and that we did not measure fungi in indoor settled dust (which might be more reflective of indoor exposure), our sampling schema might be biased toward finding outdoor fungi more influential.

We posit several explanations for the association of increased fungal concentrations with increased risk of symptoms among those without sensitization specific to the particular fungal taxon of interest. Because of the positive correlations in concentrations among some of the 4 fungal genera, a concentration increase in a specific fungus to which a subject is not sensitized might correspond with a concentration increase in another fungus to which the subject is sensitized. There might be cross-reactivity among the fungi we studied. Our fungal allergen extracts might not have produced a PST response in subjects who were indeed sensitized. The composition of fungal allergen extracts is variable.³³ Also, fungal allergen extracts are not standardized, and therefore there might be inconsistency in their ability to produce a PST response. Alternatively, we skin tested using only a single species for 3 of the 4 fungal genera evaluated, and we might have missed sensitization to other species within each genus (and we did not identify isolates to species level in the environmental samples). Finally, non–IgE-mediated effects of fungi, such as irritant effects, might also explain our findings.

The strengths of our study include the large sample size and appropriate population, atopic children with asthma. We assessed health effects combined with sensitization and exposure data and prospective evaluation of asthma outcomes rather than retrospective self-report. We used a prospective, longitudinal study design of 2 years' duration. Both indoor and outdoor exposures were taken into account, and all environmental sampling was conducted in duplicate.

Although our study is the largest examining the effects of fungi on asthma in inner-city children, we acknowledge that it has limitations. The designation of 2-mm wheal size as evidence of sensitization might be criticized as inadequate. However, when we performed the same analysis for those subjects with a wheal size of 3 mm or greater, our results did not significantly change, except for Cladosporium species, for which indoor exposure was also associated with an increase in MSDs.

Home measurements were only performed for those participants with PST responses to fungal allergen extracts. Consequently, we lack the ability to compare our findings regarding exposure or morbidity with those in children who were not sensitized to fungal allergens.

Because all subjects were reactive to at least 1 fungal allergen extract, we cannot determine whether the significant health effects are due to cross-reactivity versus non-IgE (irritant, toxigenic, and other) effects. This possibility is supported by the similar magnitude of the ORs for UVs in the PST and NST response groups.

The short sampling time and inherent variability between consecutive samples might not accurately reflect exposure over long time periods. However, it is unlikely that our sampling method would result in a spurious outcome. A failure to find any relationship between exposure and symptoms would be more likely.

Other fungi might affect asthma morbidity, but our limited skin test panel precluded us from examining their effects. The use of culture for fungal recoveries (compared, for example, with direct spore counting) limits the numbers and types of fungi recovered.

A recent study found that Alternaria species antigens are measurable, even in the absence of culturable Alternaria species.³⁴ These antigens might have been associated with nonculturable spores. Currently available methods for estimating concentrations of nonculturable spores also have limitations. Direct spore counting does not have the specificity of culture or quantitative PCR, but it enables the detection of the widest variety of spore types, including basidiospores and obligate plant pathogens, among many other potentially allergenic types. Quantitative PCR is limited by the number of fungal primers currently available, most of which are species specific and not pangeneric, and the assay can also be inhibited by a variety of chemicals, including components of airborne particulate matter.³⁵, ³⁶ We performed identification to the genus level and not to the species level; more specific identifications might have highlighted additional indoor/outdoor differences. We did not assess copollutants, which might affect responses to fungal allergens.

Our findings suggest that fungal allergen sensitization and exposure independently contribute to asthma morbidity in inner-city children with asthma and that these effects are related to exposure to outdoor fungi and indoor Penicillium species. The data support the findings of a study that demonstrated an increase in UVs and the potential value of home remediation interventions in the inner city.³⁷ The results of our study identify new possibilities for future environmental intervention strategies for this population.

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References 

1. Crain EF, Walter M, O'Connor GT, Mitchell H, Gruchalla RS, Kattan M, et al. Home and allergic characteristics of children with asthma in seven U.S. urban communities and design of an environmental intervention: the Inner-City Asthma Study. Environ Health Perspect. 2002;110:939–945
   • View In Article
   • MEDLINE
   • CrossRef
2. Health. Committee on Damp Indoor Spaces and Health. Damp indoor spaces and health. Washington (DC): National Academies Press; 2004;
   • View In Article
3. Salo PM, Arbes SJ, Sever M, Jaramillo R, Cohn RD, London SJ, et al. Exposure to Alternaria alternata in US homes is associated with asthma symptoms. J Allergy Clin Immunol. 2006;118:892–898
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (173 KB)
   • CrossRef
4. Turyk M, Curtis L, Scheff P, Contraras A, Coover L, Hernandez E, et al. Environmental allergens and asthma morbidity in low-income children. J Asthma. 2006;43:453–457
   • View In Article
   • MEDLINE
   • CrossRef
5. Su HJ, Rotnitzky A, Burge HA, Spengler JD. Examination of fungi in domestic interiors by using factor analysis: correlations and associations with home factors. Appl Environ Microbiol. 1992;58:181–186
   • View In Article
   • MEDLINE
6. Platt SD, Martin CJ, Hunt SM, Lewis CW. Damp housing, mould growth, and symptomatic health state. BMJ. 1989;298:1673–1678
   • View In Article
   • MEDLINE
   • CrossRef
7. Waegemaekers M, Van Wageningen N, Brunekreef B, Boleij JS. Respiratory symptoms in damp homes. A pilot study. Allergy. 1989;44:192–198
   • View In Article
   • MEDLINE
   • CrossRef
8. Strachan DP, Flannigan B, McCabe EM, McGarry F. Quantification of airborne moulds in the homes of children with and without wheeze. Thorax. 1990;45:382–387
   • View In Article
   • MEDLINE
   • CrossRef
9. Li CS, Hsu LY, Chou CC, Hsieh KH. Fungus allergens inside and outside the residences of atopic and control children. Arch Environ Health. 1995;50:38–43
   • View In Article
   • MEDLINE
   • CrossRef
10. Verhoeff AP, van Wijnen JH, van Reenen-Hoekstra ES, Samson RA, van Strien RT, Brunekreef B. Fungal propagules in house dust. II. Relation with residential characteristics and respiratory symptoms. Allergy. 1994;49:540–547
    • View In Article
    • MEDLINE
    • CrossRef
11. Gent JF, Ren P, Belanger K, Triche E, Bracken MB, Holford TR, et al. Levels of household mold associated with respiratory symptoms in the first year of life in a cohort at risk for asthma. Environ Health Perspect. 2002;110:A781–A786
    • View In Article
    • MEDLINE
    • CrossRef
12. Belanger K, Beckett W, Triche E, Bracken MB, Holford T, Ren P, et al. Symptoms of wheeze and persistent cough in the first year of life: associations with indoor allergens, air contaminants, and maternal history of asthma. Am J Epidemiol. 2003;158:195–202
    • View In Article
    • MEDLINE
    • CrossRef
13. Wood RA, Eggleston PA, Lind P, Ingemann L, Schwartz B, Graveson S, et al. Antigenic analysis of household dust samples. Am Rev Respir Dis. 1988;137:358–363
    • View In Article
    • MEDLINE
14. Wickman M, Gravesen S, Nordvall SL, Pershagen G, Sundell J. Indoor viable dust-bound microfungi in relation to residential characteristics, living habits, and symptoms in atopic and control children. J Allergy Clin Immunol. 1992;89:752–759
    • View In Article
    • MEDLINE
    • CrossRef
15. O'Hollaren MT, Yunginger JW, Offord KP, Somers MJ, O'Connell EJ, Ballard DJ, et al. Exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma. N Engl J Med. 1991;324:359–363
    • View In Article
    • MEDLINE
    • CrossRef
16. Beaumont F, Kauffman HF, Sluiter HJ, De Vries K. Sequential sampling of fungal air spores inside and outside the homes of mould-sensitive, asthmatic patients: a search for a relationship to obstructive reactions. Ann Allergy. 1985;55:740–746
    • View In Article
    • MEDLINE
17. Delfino RJ, Coate BD, Zeiger RS, Seltzer JM, Street DH, Koutrakis P. Daily asthma severity in relation to personal ozone exposure and outdoor fungal spores. Am J Respir Crit Care Med. 1996;154:633–641
    • View In Article
    • MEDLINE
18. Holst PE, Coleman ED, Sheridan JE, O'Donnell TV, Sutthoff PT. Asthma and fungi in the home. N Z Med J. 1983;96:718–720
    • View In Article
    • MEDLINE
19. Gergen PJ, Mitchell H, Lynn H. Understanding the seasonal pattern of childhood asthma: results from the National Cooperative Inner-City Asthma Study (NCICAS). J Pediatr. 2002;141:631–636
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (96 KB)
    • CrossRef
20. Kattan M, Mitchell H, Eggleston P, Gergen P, Crain E, Redline S, et al. Characteristics of inner-city children with asthma: the National Cooperative Inner-City Asthma Study. Pediatr Pulmonol. 1997;24:253–262
    • View In Article
    • MEDLINE
    • CrossRef
21. O'Connor GT, Walter M, Mitchell H, Kattan M, Morgan WJ, Gruchalla RS, et al. Airborne fungi in the homes of children with asthma in low-income urban communities: the Inner-City Asthma Study. J Allergy Clin Immunol. 2004;114:599–606
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (272 KB)
    • CrossRef
22. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol. 2007;120(suppl):S94–S138
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (9656 KB)
    • CrossRef
23. Evans R, Gergen PJ, Mitchell H, Kattan M, Kercsmar C, Crain E, et al. A randomized clinical trial to reduce asthma morbidity among inner-city children: results of the National Cooperative Inner-City Asthma Study. J Pediatr. 1999;135:332–338
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (181 KB)
    • CrossRef
24. Gruchalla RS, Pongracic J, Plaut M, Evans R, Visness CM, Walter M, et al. Inner City Asthma Study: relationships among sensitivity, allergen exposure, and asthma morbidity. J Allergy Clin Immunol. 2005;115:478–485
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (126 KB)
    • CrossRef
25. Morgan WJ, Crain EF, Gruchalla RS, O'Connor GT, Kattan M, Evans R, et al. Results of a home-based environmental intervention among urban children with asthma. N Engl J Med. 2004;351:1068–1080
    • View In Article
    • CrossRef
26. Hoekstra E, Samson R, Summerbell RC. Methods for the detection and isolation of fungi in the indoor environments. In:  Samson RA,  Hoekstra ES editor. Introduction to food and airborne fungi. Utrecht (The Netherlands): Centraalbureau voor Schimmelcultures; 2004;
    • View In Article
27. Chapman MD, Heymann PW, Wilkins SR, Brown MJ, Platts-Mills TA. Monoclonal immunoassays for major dust mite (Dermatophagoides) allergens, Der p I and Der f I, and quantitative analysis of the allergen content of mite and house dust extracts. J Allergy Clin Immunol. 1987;80:184–194
    • View In Article
    • MEDLINE
    • CrossRef
28. Ingram JM, Sporik R, Rose G, Honsinger R, Chapman MD, Platts-Mills TA. Quantitative assessment of exposure to dog (Can f 1) and cat (Fel d 1) allergens: relation to sensitization and asthma among children living in Los Alamos. New Mexico. J Allergy Clin Immunol. 1995;96:449–456
    • View In Article
29. Pollart SM, Mullins DE, Vailes LD, Hayden ML, Platts-Mills TA, Sutherland WM, et al. Identification, quantitation, and purification of cockroach allergens using monoclonal antibodies. J Allergy Clin Immunol. 1991;87:511–521
    • View In Article
    • MEDLINE
    • CrossRef
30. Andersen AA. New sampler for the collection, sizing, and enumeration of viable airborne particles. J Bacteriol. 1958;76:471–484
    • View In Article
    • MEDLINE
31. Arruda LK, Mann BJ, Chapman MD. Selective expression of a major allergen and cytotoxin, Asp f I, in Aspergillus fumigatus. Implications for the immunopathogenesis of Aspergillus-related diseases. J Immunol. 1992;149:3354–3359
    • View In Article
    • MEDLINE
32. Little SA, Longbottom JL, Warner JO. Optimized preparation of Aspergillus fumigatus extracts for allergy diagnosis. Clin Exp Allergy. 1993;23:835–842
    • View In Article
    • MEDLINE
    • CrossRef
33. Esch RE. Manufacturing and standardizing fungal allergen products. J Allergy Clin Immunol. 2004;113:210–215
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (149 KB)
    • CrossRef
34. Peters JL, Muilenberg ML, Rogers CA, Burge HA, Spengler JD. Alternaria measures in inner-city, low-income housing by immunoassay and culture-based analysis. Ann Allergy Asthma Immunol. 2008;100:364–369
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (220 KB)
    • CrossRef
35. Cruz P, Buttner MP. Development and evaluation of a real-time quantitative PCR assay for Aspergillus flavus. Mycologia. 2008;100:683–690
    • View In Article
    • CrossRef
36. McDevitt J, Lees P, Merz W, Schwab K. Inhibition of quantitative PCT analysis of fungal conidia associated with indoor air particulate matter. Aerobiologia. 2007;23:35–45
    • View In Article
37. Kercsmar CM, Dearborn DG, Schluchter M, Xue L, Kirchner HL, Sobolewski J, et al. Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources. Environ Health Perspect. 2006;114:1574–1580
    • View In Article
    • MEDLINE
    • CrossRef