Document Detail

Association of airborne Aspergillus with asthma exacerbation in Southern Pakistan.
Jump to Full Text
MedLine Citation:
PMID:  24809014     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Exposure to airborne fungi has been related with exacerbation of asthma in adults and children leading to increased outpatient, emergency room visits, and hospitalizations. Hypersensitivity to these airborne fungi may be an important initial predisposing factor in the development and exacerbation of asthma.
OBJECTIVE: This study was conducted to determine an association between fungal types and spore concentrations with the risk of asthma exacerbation in adults.
METHODS: This cross-sectional study was conducted from May 2008 to August 2009 at the Aga Khan University Hospital Karachi, Pakistan. All adult (age≥16 years) patients presenting to the hospital with acute asthma exacerbation were enrolled after informed consent. A home survey was conducted for each patient to assess their environmental characteristics. Indoor air samples were also obtained from the patient's home to determine the type and spore concentration of fungi within the week of their enrollment in the study.
RESULTS: Three hundred and ninety-one patients with an acute asthma exacerbation were enrolled during the study period. The mean age of participants was 46 years (standard deviation, ±18 years) and 247 (63.2%) were females. A trend of higher asthma enrollment associated with higher Aspergillus concentrations was found in two consecutive summers. A total of nineteen types of fungi were found in air samples. Aspergillus spp. was the most frequently isolated fungus with acute asthma exacerbation.
CONCLUSION: An association of higher concentration of indoor Aspergillus spp. with asthma exacerbation in adults was observed in this study.
Authors:
Ali Bin Sarwar Zubairi; Iqbal Azam; Safia Awan; Afia Zafar; Asif Ali Imam
Related Documents :
11324724 - Relationship between severity of reflux esophagitis according to the los angeles classi...
21651814 - Workers dominate male production in the neotropical bumblebee bombus wilmattae (hymenop...
22028064 - A decompositional analysis of the relative contribution of age, sex and methods of suic...
20378484 - Construction of age model for the evaluation of swallowing function using photo sensors.
9331454 - Dental caries in nineteenth century upper canada.
21846244 - Oral health status and chewing ability is related to mini-nutritional assessment result...
Publication Detail:
Type:  Journal Article     Date:  2014-04-29
Journal Detail:
Title:  Asia Pacific allergy     Volume:  4     ISSN:  2233-8276     ISO Abbreviation:  Asia Pac Allergy     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-05-08     Completed Date:  2014-05-08     Revised Date:  2014-05-12    
Medline Journal Info:
Nlm Unique ID:  101561954     Medline TA:  Asia Pac Allergy     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  91-8     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Asia Pac Allergy
Journal ID (iso-abbrev): Asia Pac Allergy
Journal ID (publisher-id): APA
ISSN: 2233-8276
ISSN: 2233-8268
Publisher: Asia Pacific Association of Allergy, Asthma and Clinical Immunology
Article Information
Download PDF
Copyright © 2014. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.
open-access:
Received Day: 10 Month: 12 Year: 2013
Accepted Day: 31 Month: 3 Year: 2014
Print publication date: Month: 4 Year: 2014
Electronic publication date: Day: 29 Month: 4 Year: 2014
Volume: 4 Issue: 2
First Page: 91 Last Page: 98
PubMed Id: 24809014
ID: 4005352
DOI: 10.5415/apallergy.2014.4.2.91

Association of airborne Aspergillus with asthma exacerbation in Southern Pakistan
Ali Bin Sarwar Zubairi1
Iqbal Azam2
Safia Awan1
Afia Zafar3
Asif Ali Imam1
1Department of Medicine, Aga Khan University, Karachi 74800, Pakistan.
2Department of Community Health Sciences, Aga Khan University, Karachi 74800, Pakistan.
3Department of Pathology and Microbiology, Aga Khan University, Karachi 74800, Pakistan.
Correspondence: Correspondence: Asif Ali Imam. Section of Pulmonary and Critical Care Medicine, Aga Khan University Hospital, Stadium Road, P.O. box 3500, Karachi 74800, Pakistan. Tel: +92-21-3486-4682, Fax: +92-21-3493-4294, aaimam@yahoo.com

INTRODUCTION

Aeroallergens, especially indoor allergens have been strongly associated with asthma and this risk is higher when the exposure is perennial [1, 2, 3, 4, 5]. Approximately 70% of asthmatics have allergic sensitization and has been reported more frequently in children [6, 7].

Indoor exposure to aerosolized fungal spores has been closely associated with sensitization and the development or exacerbation of asthma [8, 9]. The most studied fungi in relation to asthma include Alternaria, Cladosporium, Aspergillus and Penicillium spp., however these studies are mostly related to acute exposure to fungi [10, 11, 12, 13, 14].

The association of asthma with sensitization to common indoor allergens has been reported by Rhodes et al. [15]. Sensitization to fungal allergens has also been reported to be a risk factor in the development, exacerbation, severity and mortality associated with asthma [3, 16, 17]. Aspergillus spp. is now recognized to be the cause of a spectrum of allergic lower respiratory disease from asthma with fungal sensitization, severe asthma with fungal sensitization to allergic broncho-pulmonary aspergillosis [18, 19, 20, 21, 22, 23].

The primary objective of this study was to determine the role of fungi in the exacerbation of asthma in adult asthmatics. The secondary objective was to determine the spectrum of fungi in relation to the characteristics of the indoor home environment.

The study was conducted in Karachi, the largest city in Pakistan, located on the southern coast with a relatively mild climate. The city enjoys mild winters and warm summers. It receives the tail end of the monsoon rains in July and August. Previous studies of outdoor fungi in Karachi have shown a high prevalence of Aspergillus spp. throughout the year but especially during the humid summer season [24, 25]. The presence of indoor Aspergillus could be a potential cause of asthma with important implications.


MATERIALS AND METHODS
Study design and settings

This cross sectional study was conducted from May 2008 to August 2009 at the Aga Khan University Hospital in Karachi, the coastal city of Pakistan. Adult patients (age≥16 years) with an acute asthma exacerbation and residents of different parts of Karachi were enrolled (Fig. 1). Written informed consent was obtained. The study was approved by the Ethical Review Committee of the Aga Khan University.

Acute asthma exacerbation

All patients of age 16 and above who presented to the Aga Khan University Hospital with acute asthma exacerbation were screened for enrollment in the study. Acute exacerbations of asthma are episodes of a progressive increase in shortness of breath, cough, wheezing or chest tightness, or a combination of these symptoms as defined by the Global Initiative for National Asthma Guidelines [26].

Data collection

A precoded, structured questionnaire was used to collect data on demographic, socioeconomic, and health-related variables.

The lists of variables were:

  1. Demographic variables included age and gender
  2. Socioeconomic variables included occupation, number of family members, type of house, number of rooms and type of flooring
  3. Environmental variables included presence of indoor pets, plumbing leaks, overflowing trash can, dirty dishes and cooking pots, grease on or around stove, cockroach stains or droppings, live or dead cockroaches (or parts), standing water (in sink, on stove, in flower pots), evidence of any moisture or leaks, mildew on the ceiling, walls, window, musty smell, evidence of tobacco use like ashtrays or cigarette butts or smell of tobacco smoke in the room
  4. Health related variables included any previous episodes of asthma exacerbation, associated factors like respiratory tract infection, change of season, indoor smoking, allergen exposure, and site of enrollment (e.g., outpatient clinic, emergency room, or inpatient).

Home survey

A research assistant conducted a home visit within a week of enrollment. This included home inspection, environmental data collection and collection of indoor air samples.

Air sampling

Air samples were obtained by using single stage Burkard portable air sampler (Burkard Manufacturing Co., Rickmansworth, UK), which draws air through a sieve plate with 100 holes of 1-mm diameter over a petri dish containing 18 mL of agar. We used three types of media to support growth of variety of environmental fungi, named Saboraud's, cornmeal and potatodextrose agar. The plates were exposed to air sampler for a period of 60 seconds at a flow rate of 30 L per minute. Indoor air samples were collected from each patient's home within 1 week of enrollment. Outdoor air samples from three locations of the city (coastal, central and inland areas) were taken monthly during the study period.

Laboratory analysis

All specimens were submitted to Microbiology section of Clinical Laboratory at Aga Khan University. Plates were incubated at 25℃ and 37℃ for maximum of 7 days. Each plate was examined on daily basis. Total colony count was noted and fungal identification was performed by conventional laboratory methods including ability to grow at different temperature, rate of growth, color and morphological characteristics of colonies. Identification of fungi were further confirmed by microscopic examination by using Lactophenol cotton blue staining and biochemical reactions where required.

Meteorological data

Daily Minimum And Maximum Ambient Temperature And Humidity Was Obtained From The Dawn Newspaper (Epaper.Dawn. Com) [27]. This Newspaper Gets Daily Information On The Weather Conditions Of The City From Pakistan Meteorological Department Located In The City Center (Fig. 1).

Statistical analysis

Frequency distribution of household characteristics including type of accommodation, flooring type, cooking fuel, visible dampness, growth of mold, musty odor, indoor pets, and pest infestation were calculated. Line graphs were made by month of registration and average humidity (%), total monthly enrollment, median Aspergillus concentration and for other important spores as well. Descriptive statistics were computed including mean, standard deviation, minimum, maximum observations, quartiles were obtained for different fungal spore concentrations and meteorological data.

Independent samples t-test was used to observe the mean age difference between those who refused or did not refuse to participate in the study. Similarly, chi-square test was used to observe the association between participation status and gender as well as area of residence. Pearson correlation was also computed to observe the relationship between average humidity (%) and asthma exacerbation.

Data was analyzed in PASW ver. 18.0 (SPSS Inc., Chicago, IL, USA). A p value less than 0.05 was considered as statistically significant.


RESULTS

Four hundred and seventy-six patients with acute asthma exacerbations were identified, out of which 391 agreed to participate in the study (Fig. 2). The mean age of the patients was 46 years (standard deviation, ±18 years) and 247 (63.2%) were females. Characteristics of patients who refused to participate were not significantly different from participants; i.e., age (p = 0.58), gender (p = 0.34) and area of residence (p = 0.64).

The characteristics of the households of the study subjects are summarized in Table 1.

A total of nineteen genuses of fungi were isolated from the indoor samples. The common fungi were Aspergillus (99.7%), Drechslera (25.3%), Penicillium (19.9%), Mucor (19.9%), Fusarium (15.6%), and Rhizopus (10.4%). Spore counts of fungi other than Aspergillus were <100 and are summarized in Table 2. There was no association seen between the concentrations of fungi and the household characteristics.

The commonest indoor fungi were Aspergillus spp. The most frequent isolates were Aspergillus flavus and Aspergillus niger. The concentration of Aspergillus was directly proportional to the number of enrollments from May to November 2008. A weak relationship was observed between number of asthma exacerbation and Aspergillus concentration (r = 0.22). The concentration of Aspergillus was lowest from December 2008 till March 2009 which coincided with relatively low humidity. During the study period, two peaks of asthma exacerbation enrollments were observed, one in January and the second noticed both years, in the month of June and July (Fig. 3). This trend was observed in months of 2 consecutive summers where high Aspergillus concentration was found with high humidity. Association of asthma exacerbation with any other fungi was not observed, albeit their concentrations were much lower than Aspergillus spp. (Fig. 4). There was no relationship observed between average monthly humidity and enrollment of asthma exacerbation (r = 0.01, p > 0.99).

Aspergillus was seen throughout the year while certain fungi like Curvalaria were seen exclusively in autumn. The concentration of Rhizopas and Drechslera peaked in low humidity season (Fig. 4).

In the outdoor samples, nine fungi were isolated; Aspergillus, Drechslera and Penicillium outnumbered the rest on the basis of their spore concentration. The average spore concentrations were similar for the three outdoor locations (Fig. 1). The meteorological data was divided into three categories; hot and dry (April, September till October), hot and humid (May to August) and cold and dry weather (November to March). Increased enrollment in cold and dry season did not correlate with Aspergillus concentration.


DISCUSSION

In this study we found that patients with an acute exacerbation of asthma had corresponding high spore counts of Aspergillus in indoor air sampled from their homes.

We observed the trend of asthma exacerbation in adult asthmatics with increasing levels of indoor Aspergillus spp. A study by Shendell et al. [28] found a trend of association between total fungal DNA with decreased forced vital capacity and forced expiratory volume in 1 second in adults with asthma and chronic bronchitis. Similarly, Alternaria has been reported to be associated with asthma in the northern hemisphere [10].

Long-term studies of adult asthma in association with fungi are limited. Dales et al. [29] reported that higher concentrations of Alternaria, Caldosporium, Aspergillus, Epicoccum, and Ganoderma were associated with increased emergency room visits in children in Canada because of asthma. A study conducted in London from June to October (1992-93) looked at the association of outdoor fungi with asthma exacerbation in children [30]. This study showed the association of increased emergency visits and hospitalizations in children with various fungi including Alternaria, Epicoccum, Agrocybe, Basidiospores, and Ascospores. Similarly, a study by Rosas et al. [31] on environmental factors in relation to asthma hospitalization in Mexico City concluded that elevated hospital asthma admissions in children were associated with Leptospheria spp.

The winter peak enrollment seen in December 2008 and January 2009 in this study was most likely due to increased respiratory tract infection resulting in asthma exacerbations. Previous studies suggested that 50-60% of adult asthma exacerbation is associated with upper respiratory tract infections [32]. Johnston [33] showed the predictable seasonal epidemics of asthma exacerbations in winter in adults and early September in children in Canada, were mostly caused by an increase in seasonal viral infections in both children and adults.

The secondary study objective of the study was to determine the spectrum of fungi in relation to the characteristics of the indoor home environment and the effect of temperature, humidity and seasonal variation. There is evidence of an association between respiratory tract symptoms like cough and wheezing with damp indoor environment [34]. In this study, Aspergillus spp. was found in most homes of asthmatic patients in all seasons with relatively high concentration in summers, while other fungi were found in certain seasons in low concentration. The presence of such high levels of air-borne Aspergillus spp. in adult asthmatic homes has not been reported previously. Previous data of fungi in Karachi has shown high levels of outdoor Aspergillus spp. during the hot and humid summer season [24, 25].

Previous studies, mostly in the United States, United Kingdom, and Northern Europe have shown the association of dampness and molds in homes with adverse respiratory effects among adults and children [35]. We did not find any association between particular home characteristic or dampness with any fungus in this study in Southern Pakistan.

The role of indoor allergens as a constant source of exposure, sensitization and development of asthma is considered important in the case of house dust mite, cockroach and pet allergy. The association of constant exposure to fungi as a causal agent of asthma has not been well studied but could be important in regions with high indoor fungi prevalence. The finding of Aspergillus spp. all year round in the homes of adult asthmatics could have important implications. This study looks at the spatial relationship of Aspergillus spp. with asthma exacerbation.

An incidental finding was a dominance of female asthmatics in the study. Although this is consistent with previous data on the gender preponderance in asthma, no specific environmental factor causing this phenomenon was identified. The women in this region are usually housewives, spending more time at home, where dampness could be associated with increased fungal concentrations leading to asthma exacerbation [34, 35]. Respiratory symptoms have been associated with wood smoke exposure in women in Southern Pakistan [36] while in urban population natural gas is a source of fuel for cooking. Previous studies have suggested both hormonal and environmental influences are possible causes of this predilection among females [37, 38].

The strength of the study is that it provides data on a region, which has been under studied in the past. This study provides new information on the possibility of Aspergillus spp. as an important trigger of asthma and enabled us to correlate the climatic effect on the concentration of Aspergillus and asthma exacerbations in two consecutive summer months of June and July.

A limitation of this study is the lack of specific sensitization data of the patients such as allergy skin tests and specific immunoglobulin E levels. Another limitation of study was the lack of objective laboratory confirmation of the possibility of upper respiratory tract infections as a cause of increased patient enrollment in winter season. The lack of a control group is also a limitation of the study, which is an important criteria to observe the risk factors related to the disease.

In conclusion, in this study population an association between higher concentration of indoor Aspergillus spp. and asthma exacerbation in adults was found. We suggest that future studies need to be conducted to see the contributing role of dust mite, cockroach and other air pollutants.


ACKNOWLEDGEMENTS

We are thankful to Dr. Kiran Afshan, Mr. Shakeel Ahmed, and Dr. Umar Khan for data collection. Home survey was completed by Mr. Shakeel Ahmed.


References
1. Knutsen AP,Bush RK,Demain JG,Denning DW,Dixit A,Fairs A,Greenberger PA,Kariuki B,Kita H,Kurup VP,Moss RB,Niven RM,Pashley CH,Slavin RG,Vijay HM,Wardlaw AJ. Fungi and allergic lower respiratory tract diseasesJ Allergy Clin ImmunolYear: 201212928029122284927
2. Rosenstreich DL,Eggleston P,Kattan M,Baker D,Slavin RG,Gergen P,Mitchell H,McNiff-Mortimer K,Lynn H,Ownby D,Malveaux F. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthmaN Engl J MedYear: 1997336135613639134876
3. O'Hollaren MT,Yunginger JW,Offord KP,Somers MJ,O'Connell EJ,Ballard DJ,Sachs MI. Exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthmaN Engl J MedYear: 19913243593631987459
4. Targonski PV,Persky VW,Ramekrishnan V. Effect of environmental molds on risk of death from asthma during the pollen seasonJ Allergy Clin ImmunolYear: 1995955 Pt 19559617751516
5. Black PN,Udy AA,Brodie SM. Sensitivity to fungal allergens is a risk factor for life-threatening asthmaAllergyYear: 20005550150410843433
6. Cruz AA,Bousquet J,Khaltaev NG. Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approachGenevaWorld Health OrganizationYear: 2007
7. Kalliel JN,Goldstein BM,Braman SS,Settipane GA. High frequency of atopic asthma in a pulmonary clinic populationChestYear: 198996133613402582840
8. Institute of Medicine (US)Committee on Damp Indoor Spaces and HealthDamp indoor spaces and healthWashington, DCNational Academies PressYear: 2004
9. Douwes J,Pearce N. Invited commentary: is indoor mold exposure a risk factor for asthma?Am J EpidemiolYear: 200315820320612882941
10. Salo PM,Arbes SJ Jr,Sever M,Jaramillo R,Cohn RD,London SJ,Zeldin DC. Exposure to Alternaria alternata in US homes is associated with asthma symptomsJ Allergy Clin ImmunolYear: 200611889289817030243
11. Bush RK,Prochnau JJ. Alternaria-induced asthmaJ Allergy Clin ImmunolYear: 200411322723414767434
12. Pulimood TB,Corden JM,Bryden C,Sharples L,Nasser SM. Epidemic asthma and the role of the fungal mold Alternaria alternataJ Allergy Clin ImmunolYear: 200712061061717624415
13. O'connor GT,Walter M,Mitchell H,Kattan M,Morgan WJ,Gruchalla RS,Pongracic JA,Smartt E,Stout JW,Evans R,Crain EF,Burge HA. Airborne fungi in the homes of children with asthma in low-income urban communities: The Inner-City Asthma StudyJ Allergy Clin ImmunolYear: 200411459960615356564
14. Bernton HS. Asthma due to a mold-aspergillus fumigatusJAMAYear: 193095189191
15. Rhodes HL,Thomas P,Sporik R,Holgate ST,Cogswell JJ. A birth cohort study of subjects at risk of atopy: twenty-two-year followup of wheeze and atopic statusAm J Respir Crit Care MedYear: 200216517618011790650
16. Singh AM,Busse WW. Asthma exacerbations. 2: aetiologyThoraxYear: 20066180981616936237
17. Zureik M,Neukirch C,Leynaert B,Liard R,Bousquet J,Neukirch F. European Community Respiratory Health SurveySensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health surveyBMJYear: 200232541141412193354
18. Hinson KF,Moon AJ,Plummer NS. Broncho-pulmonary aspergillosis; a review and a report of eight new casesThoraxYear: 1952731733313015523
19. Schwartz HJ,Greenberger PA. The prevalence of allergic bronchopulmonary aspergillosis in patients with asthma, determined by serologic and radiologic criteria in patients at riskJ Lab Clin MedYear: 19911171381421993855
20. Maurya V,Gugnani HC,Sarma PU,Madan T,Shah A. Sensitization to Aspergillus antigens and occurrence of allergic bronchopulmonary aspergillosis in patients with asthmaChestYear: 20051271252125915821202
21. Denning DW,O'Driscoll BR,Hogaboam CM,Bowyer P,Niven RM. The link between fungi and severe asthma: a summary of the evidenceEur Respir JYear: 20062761562616507864
22. Kauffman HF,Tomee JF,van de Riet MA,Timmerman AJ,Borger P. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine productionJ Allergy Clin ImmunolYear: 20001056 Pt 11185119310856154
23. Agarwal R,Gupta D. Severe asthma and fungi: current evidenceMed MycolYear: 201149Suppl 1S150S15720662637
24. Rao TA,Shaikh AH,Ahmed M. Airborne fungal flora of Karachi, PakistanPak J BotYear: 20094114211428
25. Afzal M,Mehdi FS. Atmospheric fungi of Karachi cityPak J Biol SciYear: 20025707709
26. The Global Initiative for AsthmaGINA report: global strategy for asthma management and prevention. Updated 2012 [Internet]The global initiative for asthmaYear: c2012cited 2012 Dec 10 Available from: http://www.ginasthma.org/documents/4.
27. Pakistan Meteorological Department, Government of Pakistan [Internet]IslamabadPakistan Meteorological Department, Government of PakistanYear: c20122012 Dec 10 Available from: http://www.pmd.gov.pk/.
28. Shendell DG,Mizan SS,Yamamoto N,Peccia J. Associations between quantitative measures of fungi in home floor dust and lung function among older adults with chronic respiratory disease: a pilot studyJ AsthmaYear: 20124950250922715909
29. Dales RE,Cakmak S,Burnett RT,Judek S,Coates F,Brook JR. Influence of ambient fungal spores on emergency visits for asthma to a regional children's hospitalAm J Respir Crit Care MedYear: 20001622087209011112119
30. Atkinson RW,Strachan DP,Anderson HR,Hajat S,Emberlin J. Temporal associations between daily counts of fungal spores and asthma exacerbationsOccup Environ MedYear: 20066358059016551756
31. Rosas I,McCartney HA,Payne RW,Calderon C,Lacey J,Chapela R,Ruiz-Velazco S. Analysis of the relationships between environmental factors (aeroallergens, air pollution, and weather) and asthma emergency admissions to a hospital in Mexico CityAllergyYear: 1998533944019574882
32. Nicholson KG,Kent J,Ireland DC. Respiratory viruses and exacerbations of asthma in adultsBMJYear: 19933079829868241910
33. Johnston NW. The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbationsProc Am Thorac SocYear: 2007459159618073388
34. Fisk WJ,Lei-Gomez Q,Mendell MJ. Meta-analyses of the associations of respiratory health effects with dampness and mold in homesIndoor AirYear: 20071728429617661925
35. Mendell MJ,Mirer AG,Cheung K,Tong M,Douwes J. Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidenceEnviron Health PerspectYear: 201111974875621269928
36. Siddiqui AR,Lee K,Gold EB,Bhutta ZA. Eye and respiratory symptoms among women exposed to wood smoke emitted from indoor cooking: a study from southern pakistanEnergy Sustain DevYear: 200595866
37. Chen Y,Stewart P,Johansen H,McRae L,Taylor G. Sex difference in hospitalization due to asthma in relation to ageJ Clin EpidemiolYear: 20035618018712654413
38. Schatz M,Clark S,Camargo CA Jr. Sex differences in the presentation and course of asthma hospitalizationsChestYear: 2006129505516424412

Article Categories:
  • Original Article

Keywords: Aspergillus, Asthma, Fungal spores, Pakistan.

Previous Document:  Pholcodine consumption and immunoglobulin E-sensitization in atopics from Australia, Korea, and Japa...
Next Document:  Association of insulin resistance with bronchial hyperreactivity.