Charles S. Barnes

Health effects of indoor fungi

OBJECTIVE To review the nontoxic harmful effects that poor indoor air quality caused by fungi can have on health. DATA SOURCES We searched PubMed for publications related to the various topics discussed in this review, and we relied on our knowledge of the field. STUDY SELECTION Where more than one publication was relevant, we attempted to identify a consensus of the reports and cited the most relevant articles. Priority was given to randomized controlled trials and expert reports when available, although much of the information herein relates to laboratory research. RESULTS Actively growing fungal colonies can release volatile substances that have an unpleasant smell, leading to psychological responses in the occupants such as fatigue and nausea. Symptoms that are likely caused by indoor fungi include respiratory complaints that involve the nose and lungs, eye symptoms, and mucous membrane irritation. These adverse effects can occur by a variety of mechanisms, including IgE-mediated hypersensitivity, fungal infection, irritant reaction to spores or fungal metabolites, and possibly toxic reaction to mycotoxins. CONCLUSIONS Reduced fungal exposure can reasonably be expected to improve health. Removal of moisture from the indoors and proper maintenance of air filters can aid in prevention and elimination of fungi from the home environment. Small areas of present contamination can be cleaned with a dilute bleach solution, which kills viable colonies and removes their mycelia. If fungal contamination is not addressed early, substantial damage can occur, requiring professional remediation. Above all, the individual should not panic at the first sight of fungi growing in the home. Regular inspection and cleaning can prevent many fungus-related problems.

Environmental assessment and exposure control of dust mites: a practice parameter

Jay Portnoy, MD; Jeffrey D. Miller, MD; P. Brock Williams, PhD; Ginger L. Chew, ScD *; J. David Miller, PhD; Fares Zaitoun, MD; Wanda Phipatanakul, MD, MS; Kevin Kennedy, MPH; Charles Barnes, PhD; Carl Grimes, CIEC; Desiree Larenas-Linnemann, MD; James Sublett, MD; David Bernstein, MD; Joann Blessing-Moore, MD; David Khan, MD; David Lang, MD; Richard Nicklas, MD; John Oppenheimer, MD; Christopher Randolph, MD; Diane Schuller, MD; Sheldon Spector, MD; Stephen A. Tilles, MD; and Dana Wallace, MD Chief Editors: Jay Portnoy, MD; Jeffrey D. Miller, MD; P. Brock Williams, PhD; Ginger L. Chew, ScD* Members of the Joint Taskforce on Practice Parameters: David Bernstein, MD; Joann Blessing-Moore, MD; David Khan, MD; David Lang, MD; Richard Nicklas, MD; John Oppenheimer, MD; Jay Portnoy, MD; Christopher Randolph, MD; Diane Schuller, MD; Sheldon Spector, MD; Stephen A. Tilles, MD; Dana Wallace, MD

Environmental assessment and exposure control: a practice parameter—furry animals

Members of the Joint Task Force onPractice Parameters:David Bernstein,MD, Joann Blessing-Moore,MD, Linda Cox,MD, David Khan,MD, David Lang,MD, RichardNicklas, MD, John Oppenheimer, MD, Jay Portnoy, MD, Christopher Randolph, MD, Diane Schuller, MD, Sheldon Spector, MD, Stephen A. Tilles, MD, Dana Wallace, MD Practice ParameterWork Group: James Sublett, MD, cochair, Kevin Kennedy, MPH, cochair, Charles Barnes, PhD, David Bernstein, MD, Jonathan Bernstein, MD, Carl Grimes, Elizabeth Matsui, MD, Jeffrey D. Miller, MD, J. David Miller, PhD, Wanda Phipatanakul, MD, MS, James Seltzer, MD, P. Brock Williams, PhD Invited Reviewers: Jack Armstrong, Hans Gr×nlund, PhD, Kraig W. Jacobson, MD, Jill A. Poole, MD, Matthew A Rank, MD, Megan Taylor, MD This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthmaand Immunology, and the Joint Council of Allergy, Asthmaand Immunology. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing “Environmental Assessment and Remediation: A Practice Parameter.” This is a complete and comprehensive document at the current time. The medical environment is a changingenvironment, andnotall recommendationswillbeappropriate forallpatients.Because thisdocument incorporatedtheeffortsofmanyparticipants,nosingle individual, including thosewhoservedontheJointTaskForce, isauthorizedtoprovideanofficialAAAAIorACAAIinterpretationofthesepracticeparameters.Anyrequestforinformationaboutoraninterpretation of these practice parameters by the AAAAI or ACAAI should be directed to the executive offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use bypharmaceutical companies in drugpromotion. Reprints: Joint Council of Allergy, Asthmaand Immunology, 50NBrockway St, #3-3 Palatine, IL 60067. Disclosures: The following is a summaryof interests disclosedonWorkGroupmembers’ Conflict of InterestDisclosure Statements (not including information concerning familymember interests). Completed Conflict of Interest Disclosure Statements are available on request. Dr. Sublett is the owner of AllergyZone. Dr. Portnoy is a speaker and consultant for ThermoFisher (Phadia). Dr. Barnes is a consultant for and has received research funding from Clorox Corporation. Mr. Grimes is the owner of Healthy Habitats LLC. Dr. Matsui is speaker for Indoor BioTechnologies.Dr.Miller is theownerofMission:Allergy Inc.Dr. Seltzer is thePresident of JamesM. Seltzer, Assoc. TheotherWorkGroupmembershaveno conflicts todisclose. The Joint Task Force recognizes that experts in a field are likely to have interests that could come into conflictwith development of a completely unbiased and objective practice parameter. To take advantage of that expertise, a process has beendeveloped to prevent potential conflicts from influencing thefinal document in a negativeway. At theworkgroup level,memberswhohaveapotential conflictof interest eitherdonotparticipate indiscussions concerning topics related to thepotential conflictor, if theywrite a section onthattopic, theworkgroupcompletelyrewritesitwithouttheir involvementtoremovepotentialbias. Inaddition,theentiredocumentisreviewedbytheJointTaskForce,andanyapparent bias is removedat that level. Finally, thepracticeparameter is sent for reviewbothby invited reviewersandbyanyonewithan interest in the topicbyposting thedocumenton thewebsites of theACAAI and theAAAAI. In particular, the 2 owners of companies that produce products discussed in this practice parameter are Jeffrey D. Miller, MD, and James Sublett, MD. DrMiller wrote an initial section on mattress encasings. This section was then completely rewritten by other members of the work groupwithout his participation. Dr Sublett wrote a preliminary draft of the section on air filtration. That sectionwas also subsequently rewritten by othermembers of thework groupwithout his participation. Neither participant provided subsequent input into those sections. The Joint Task Force has made a concerted effort to acknowledge all contributors to this parameter. If any contributors have been excluded inadvertently, the Task Force will ensure that appropriate recognition of such contributions ismade subsequently. Work Group Cochairs: James Sublett,MD, FamilyAllergy andAsthma, Louisville, Kentucky; KevinKennedy,MPH, Center for EnvironmentalHealth, Children’sMercyHospitals C JointTaskForceLiaison:JayM.Portnoy,MD,SectionofAllergy,Asthma& Immunology, TheChildren’sMercyHospitalsC JointTaskForceMembers:David I. Bernstein,MD,DepartmentofClinical,MedicineandEnvironmentalHealth,Division ofAllergy/Immunology,UniversityofCincinnati,CollegeofMedicine,Cincinnati,Ohio; JoannBlessing-Moore,MD,Departmentof Immunology,StanfordUniversityMedicalCenter,PaloAlto, California; Linda Cox, MD, Department of Medicine, Nova Southeastern University College of Osteopathic Medicine, Davie, Florida; David A. Khan, MD, Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, Texas; David M. Lang, MD, Allergy/Immunology Section, Division of Medicine, Allergy and Immunology Fellowship Training Program, Cleveland Clinic Foundation, Cleveland, Ohio; Richard A. Nicklas, MD, Department of Medicine, George Washington Medical Center, Washington, DC; John Oppenheimer, MD, Departmentof InternalMedicine,NewJerseyMedicalSchool,PulmonaryandAllergyAssociates,Morristown,NewJersey; JayM.Portnoy,MD,SectionofAllergy,AsthmaI Christopher C. Randolph, Department of Pediatrics,YaleAffiliatedHospitals,Center forAllergy,Asthma,IDianeE.Schuller,MD,DepartmentofPediatrics,PennsylvaniaStateUniversityMilton S.HersheyMedical College,Hershey, Pennsylvania; SheldonL. Spector,MD,DepartmentofMedicine,UCLASchool ofMedicine, LosAngeles, California; StephenA. Tilles,MD,Departmentof Medicine,UniversityofWashington,SchoolofMedicine,Redmond,Washington;DanaWallaceMD,DepartmentofMedicine,NovaSoutheasternUniversityCollegeofOsteopathicMedicine, Davie, Florida;ParameterWorkGroupMembers:CharlesBarnes,PhD,AllergyResearch,TheChildren’sMercyHospitalsCDavid I.Bernstein,MD,Department of Clinical Medicine, Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, Ohio; Jonathan A. Bernstein, MD, Department of Internal Medicine, Division of Immunology/Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio; Carl Grimes, CIEC, Healthy Habitats LLC, Denver, Colorado; Elizabeth Matsui, MD, MHS, Department of Pediatrics, Johns Hopkins School ofMedicine, Baltimore,Maryland; Jeffrey D.Miller, MD, Department of Pediatrics, NewYorkMedical College, Valhalla, NewYork; J. David Miller,PhD,DepartmentofBiochemistry,CarltonUniversity,Ottawa,Ontario,Canada;WandaPhipatanakul,MD,MS,DepartmentofPediatrics,DivisionofAllergyandImmunology,Harvard Medical School, Children’s Hospital Boston, Boston, Massachusetts; JamesM. Seltzer, MD, RelianceMedical Group, Department of Allergy and Immunology,Worcester, Massachusetts; P. BrockWilliams,PhD,DepartmentofAllergy/Immunology,UniversityofMissouri–KansasCitySchoolofMedicineandTheChildren’sMercyHospitalsC Invited Reviewers: Jack Armstrong, MD, Medical Arts Allergy, P.C., Carlisle, Pennsylvania; Hans Gr×nlund, PhD, Department of Immunology, Clinical Immunology and Allergy Unit Karolinska Institute,Stockholm,Sweden;KraigW.Jacobson,MD,CPI,OregonAllergyAssociates,AllergyandAsthmaResearchGroup,Eugene,Oregon;JillA.Poole,MD,DepartmentofMedicine,Division ofAllergy, Asthma& Immunology,University ofNebraskaMedical Center,Omaha,Nebraska;MatthewARank,MD,DivisionofAllergicDiseases,MayoClinic, Rochester,Minnesota;Megan Taylor,MD, Allergy&AsthmaCare, Jenkintown, Pennsylvania.

Practice parameterEnvironmental assessment and exposure control of dust mites: a practice parameter

Jay Portnoy, MD; Jeffrey D. Miller, MD; P. Brock Williams, PhD; Ginger L. Chew, ScD *; J. David Miller, PhD; Fares Zaitoun, MD; Wanda Phipatanakul, MD, MS; Kevin Kennedy, MPH; Charles Barnes, PhD; Carl Grimes, CIEC; Desiree Larenas-Linnemann, MD; James Sublett, MD; David Bernstein, MD; Joann Blessing-Moore, MD; David Khan, MD; David Lang, MD; Richard Nicklas, MD; John Oppenheimer, MD; Christopher Randolph, MD; Diane Schuller, MD; Sheldon Spector, MD; Stephen A. Tilles, MD; and Dana Wallace, MD Chief Editors: Jay Portnoy, MD; Jeffrey D. Miller, MD; P. Brock Williams, PhD; Ginger L. Chew, ScD* Members of the Joint Taskforce on Practice Parameters: David Bernstein, MD; Joann Blessing-Moore, MD; David Khan, MD; David Lang, MD; Richard Nicklas, MD; John Oppenheimer, MD; Jay Portnoy, MD; Christopher Randolph, MD; Diane Schuller, MD; Sheldon Spector, MD; Stephen A. Tilles, MD; Dana Wallace, MD

Allergenic materials in the house dust of allergy clinic patients

INTRODUCTION Environmental agents including animal, fungal, tree, and weed antigens are known to cause allergic rhinitis and asthma. The following study was performed to measure the antigen concentration of several of these in house dust of children seen in an allergy clinic. Comparisons are made between household allergen levels of children seen for asthma and children seen for other reasons. METHODS Dust samples were solicited from patients in a pediatric allergy specialty clinic and other individuals associated with the clinic. Persons submitting dust were asked to complete a questionnaire describing their house. Samples were extracted, centrifuged, and filtered for sterility. Samples were stored in 50% glycerol at -20 degrees C. Specific antigens for Alternaria, Cladosporium, Aspergillus, Candida, Dermatophagoides farinae, cat, dog, oak, fescue, ragweed, plantain, and cockroach were measured using inhibition assays developed with whole antigen extract. Allergens Der p1, Der f 1, Alt a 1, and Alt a 70 kD were measured using double monoclonal antibody assays. RESULTS Significant concentrations of whole antigen from cat, dog, oak, Alternaria, and Cladosporium were detected. Between 0.1 and 18 microg of Der f1 and Der p1 per gram of dust were also measured. Alt a 1 and Alt a 70 kD levels varied between 3.0 and 1000 U/g of dust. Significant positive correlations were observed in levels of dust mite and Alternaria allergen for patients with an evaluation of asthma. CONCLUSIONS We found measurable levels of fungal antigens (Alternaria, Cladosporium), mite antigens, and animal antigens (dog and cat) in the majority of dust samples in this self-selected set of allergy clinic patients. Specific allergens Alt a 1, Alt a 70kD, and Der p 1 were significantly higher in the homes of asthmatic patients when compared with patients seen for reasons other than asthma. These studies support the hypothesis that fungal allergen exposure is an important component in the pathogenesis of the clinical condition known as asthma.

Evaluation of Four Bioaerosol samplers in the Outdoor Environment

INTRODUCTION A comparative evaluation of four air samplers was performed using bioaerosol collection in the outdoor environment. METHODS Test samplers used included a Rotorod, a Kramer-Collins suction trap, an all-glass impinger (AGI-30), and a high-volume cyclonic liquid impinger (SpinCon). All samples were analyzed microscopically for spores and pollen. The two collectors providing a liquid sample (AGI-30 and SpinCon) also were analyzed for specific allergen content by enzyme-linked immunoassay. RESULTS The SpinCon collected a larger number of spores than the other devices. The number of spores collected by this unit per volume of air sampled was comparable to the AGI-30. The Rotorod and Kramer-Collins collected a lower number of spores per unit of air but collected a larger number of pollen grains per volume sampled. Alternaria allergens Alt a I and GP70 were collected by both liquid impingers; however, the SpinCon collected more Alt a I and the AGI-30 collected more GP70. CONCLUSIONS The SpinCon is a device that is capable of efficiently sampling a high volume of air and concentrating it in a form that can be analyzed for the presence of spores and fungal allergens. It is less useful for collecting intact pollen grains. Pollen allergen quantitation has not yet been performed on the SpinCon effluent.

Comparison of outdoor allergenic particles and allergen levels

INTRODUCTION Spore and pollen counts have been used traditionally to determine aeroallergen exposure. Using a liquid based collector and enzyme immunoassays, we have developed methods for measuring airborne allergen concentrations. In this work we test the hypothesis that airborne allergen concentrations are directly related to spore and pollen counts. METHODS Test samplers used included a high-volume cyclonic liquid impinger (SpinCon) and a standard spore trap (Burkard). Samples were collected on a weekly basis from May to October and were analyzed microscopically for spores and pollen grains. The liquid samples were analyzed by enzyme-linked immunoassay for the presence of allergens from Alternaria, Cladosporium, Aspergillus, oak, fescue, ragweed, and plantain. Specific Alternaria allergens Alt al and GP70 also were measured. RESULTS Pollen counts for the SpinCon and Burkard collectors were similar, though spore counts were lower with the SpinCon. Detectable amounts of three of the seven allergenic species including fescue, ragweed, and Alternaria were present in air samples. Concentrations of pollens were seen in their respective seasons while fungal allergen levels varied throughout the period. Allergen levels generally agreed with particle counts, however peak allergen levels and peak particle counts for individual species did not correlate well. CONCLUSIONS At flow rates of 236 L/min, the SpinCon is comparable to the Burkard for counting airborne pollen and spores. Samples collected by the SpinCon permit quantitative determination of allergen levels in outdoor air. The poor correlation between measured airborne allergen and related particles indicates the potential for significant allergen exposure in the absence of identifiable particles in air.

Maintenance dosing for sublingual immunotherapy by prominent European allergen manufacturers expressed in bioequivalent allergy units

BACKGROUND Sublingual immunotherapy (SLIT) has become established in Europe, and its efficacy is being evaluated in the United States. The doses used for SLIT in Europe today are difficult to evaluate, because each manufacturer expresses the potency of its extracts differently. OBJECTIVES To compare in vitro European SLIT maintenance solutions against US licensed standardized allergenic extract concentrates and to determine the monthly SLIT doses delivered expressed in bioequivalent allergy units ([B]AU). METHODS We studied Dermatophagoides pteronyssinus, timothy grass pollen, cat (hair) and short ragweed pollen allergen extracts. The SLIT maintenance solutions of 4 leading European manufacturers and standardized concentrate extracts of 3 US manufacturers were analyzed with the following assays: protein content, relative potency (immunoglobulin E [IgE]-binding enzyme-linked immunosorbent assay [ELISA] inhibition) and major allergen content. The relative monthly allergen dose in (B)AU was calculated for each recommended SLIT schedule. RESULTS Relative potency was approximately 10 times higher for US concentrate standardized extracts-which are meant to be diluted-than for European SLIT maintenance solutions of D pteronyssinus and timothy grass pollen. For cat (hair) and short ragweed pollen, the difference was less. Measurements of relative potency and major allergen content correlated well. In our assays, European mite extracts contain a very low quantity of Der p 2 compared with US mites. CONCLUSION Recommended SLIT doses in Europe vary widely among the manufacturers, but are consistently lower (Eur1) or higher (Eur4) over all four allergens tested. SLIT efficacy probably depends on additional factors apart from the exact dose. SLIT dose finding studies should be done for each product.

IgE-reactive proteins from Stachybotrys chartarum.

BACKGROUND Stachybotrys chartarum has been associated with idiopathic pulmonary hemorrhage in infants. This is thought to be mycotoxin-related. There are increasing numbers of reports linking this fungus to the indoor environment of patients with other pulmonary problems, including allergies and asthma. OBJECTIVE Given the potential significance of this fungus as a pulmonary pathogen, this work evaluates the antigenic proteins of S. chartarum as to their molecular size and the prevalence of immunoglobulin (Ig)E and IgG directed against them in the general population. METHODS S. chartarum was isolated from a local home. S. chartarum for extract production was grown on minimum salts and glucose. Plasma from 132 healthy individuals was evaluated for IgE and IgG directed against S. chartarum using direct and inhibition enzyme immunoassay. The number and molecular size of those proteins that were bound by IgE from pooled sera known to contain IgE to S. chartarum were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting. RESULTS Enzyme immunoassay indicated 65 of 132 (49.2%) sera tested contained IgG against S. chartarum and 13 of 139 (9.4%) sera tested contained IgE against S. chartarum. Pooled sera identified two IgE-binding proteins from extracts of S. chartarum spores and mycelia. These proteins are 34 and 52 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblot. CONCLUSIONS We conclude sensitivity to S. chartarum is potentially much more widespread than previously appreciated. This fungus may impact the asthmatic and allergic population through both immunologic and toxic mechanisms. Its significance in the milieu of allergenic fungi may need to be re-evaluated.

The effect of temperature, relative humidity and rainfall on airborne ragweed pollen concentrations

Major weather parameters have long been known to alter airborne pollen and spore concentrations. The following study was conducted to study the effect of three of these parameters on airborne ragweed pollen concentrations.During the ragweed (RW) season for the years 1997 and 1998, 10 minute pollen collections were taken at least every 4 hours using an Allergenco MK-3 spore trap. Slides were fixed, and counted microscopically at 400X. During this same period, weather parameters were monitored by an Automated Weather Systems recording station located within a few meters of the collector.The ragweed season for this region begins in mid August and ends by mid October. Temperature patterns for the period demonstrated usual daily fluctuations with highs 13 to 35 °C and lows 8 to 24 °C. Relative humidity readings for the period varied between 25 and 100%. Highest RW values were seen after seasonal cooling in September. Daily rainfall for the period varied between 0 and 100 mm. Airborne RW always declined sharply after strong rainfall events (> 10 mm/day). Peak airborne RW concentrations were often associated with the passing of frontal boundaries and the change in wind direction and velocity that accompanies that passing.Factors influencing airborne RW concentrations are multiple and complex, but atmospheric forces have great influence. The passing of major weather fronts and the associated temperature drops, wind disturbances and rainfall are the major factors.