P. Brock Williams

Latex allergen in respirable particulate air pollution

OBJECTIVE Urban air samples contain numerous irregular respirable black particles, which may be airborne tire fragments. A major component of tires is natural latex. Proteins of natural latex can act as adjuvants and as antigens capable of eliciting immediate hypersensitivity, making their presence in particulate air pollution an important clinical issue. METHODS Particulate air pollutants were collected by volumetric sampling devices and characterized by optical microscopy, chemical solubility tests, and mass spectrometry. Extracts of rubber tire fragments were tested for elutable latex antigens by antibody inhibition assays. RESULTS Identification of latex in air samples and milled material from automobile tires was supported by mass spectrometry results and was further confirmed by physical appearance and chemical solubility studies. Competitive immunoassay confirmed the presence of extractable latex antigens from rubber tire fragments. CONCLUSIONS Latex antigens are extractable from rubber tire fragments, which are abundant in urban air samples. Given the adjuvant and sensitizing effects of latex, these airborne particles could contribute, through direct and indirect mechanisms, to the increase in both latex sensitization and asthma. The impact of these particles should be considered in the issue of morbidity and mortality rates associated with respiratory diseases and air pollution.

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

A blinded, multi-center evaluation of two commercial in vitro tests for latex-specific IgE antibodies

PURPOSE To compare the diagnostic value of two commercial in vitro tests for the detection of latex-specific IgE antibodies. METHODS Serum samples were collected from latex-allergic and nonlatex-allergic individuals. Persons were classified as latex allergic if they had a positive clinical history and a positive skin prick test with a latex extract. Persons with no latex-related symptoms and negative skin tests were classified as nonlatex allergic. The serum samples were tested in a blinded fashion by a laboratory using the CAP (Pharmacia-Upjohn) and AlaSTAT (Diagnostic Products Company) assays. Values of 0.35 kA U/L or greater were considered positive in both tests. RESULTS The 143 sera studied came from 83-latex allergic and 60 nonallergic persons. The in vitro tests were found to have sensitivities of 79.5% and 73.8%, and specificities of 90.2% and 91.7%, for CAP and AlaSTAT, respectively. The positive predictive values were 91.7% and 92.5%, while the negative predictive values were 76.4% and 71.4% for the CAP and AlaSTAT, respectively. CONCLUSION In individuals classified by the combination of clinical history and skin test results, both the Pharmacia CAP and the DPC AlaSTAT demonstrated acceptable sensitivities, specificities, and predictive values for detection of antilatex IgE antibodies. These findings suggest that both assays can be useful adjuncts to the diagnosis of latex allergy.

Endotoxin as a Factor in Adverse Reactions to Latex Gloves

BACKGROUND Endotoxin is an inflammatory made by gram negative bacteria that can irritate the skin, induce respiratory problems, fever, and shock. It is an adjuvant for both delayed hypersensitivity and IgE production and has been shown to magnify antigen specific mediator release. Since many of the clinical problems associated with natural latex products involve similar clinical sequelae, we investigated the possibility that latex gloves might be contaminated with endotoxin. OBJECTIVE To measure the endotoxin content of a variety of natural latex gloves, investigate the its distribution and origin, associated with latex proteins, and determine the particle sizes associated with its release. METHODS Endotoxin, protein, and allergen were measured using a quantitative kinetic Limulus assay, modified Lowry, and RAST inhibition, respectively. Particle size and density were determined using an Anderson multistage air sampler and CsCl2 gradient. RESULTS Endotoxin was found to be a highly significant contaminant of some latex gloves. Levels ranged from 0.09 ng to 2.8 micrograms/g of glove. Protein levels ranged from < 25 to 1150 micrograms/g of glove while allergen levels ranged from < 1 to 837 micrograms/g of glove. Endotoxin and protein eluted rapidly from the interior of the gloves tested. Greater than 70% of the endotoxin was found to be associated with particles in the < 7 microns aerodynamic diameter range. The highest levels of endotoxin were found in nonsterile examination gloves with a tendency towards powdered gloves containing more endotoxin and protein. A slurry containing cross-linked dextran through which gloves were dipped revealed very high endotoxin contamination (64 micrograms/mL) while unused cross-linked dextran has very little associated endotoxin. CONCLUSIONS These data demonstrate that some natural rubber latex gloves, particularly nonsterile examination gloves, are contaminated with high amounts of endotoxin and proteins. These were found mostly on the inside of gloves and were released as very small respirable particles that were not physically associated with the powder. These findings support the hypothesis that endotoxin may be responsible for some of the tissue irritation associated with latex glove use. In addition, this material may be responsible for the enhancement of delayed and immediate hypersensitivity reactions to chemicals and proteins found in these products and offers a possible explanation for the disproportionate severity of these reactions.

Exposure and Health Effects of Fungi on Humans

Fungi are ubiquitous microorganisms that are present in outdoor and indoor environments. Previous research has found relationships between environmental fungal exposures and human health effects. We reviewed recent articles focused on fungal exposure and dampness as risk factors for respiratory disease development, symptoms, and hypersensitivity. In particular, we reviewed the evidence suggesting that early exposure to dampness or fungi is associated with the development of asthma and increased asthma morbidity. Although outdoor exposure to high concentrations of spores can cause health effects such as asthma attacks in association with thunderstorms, most people appear to be relatively unaffected unless they are sensitized to specific genera. Indoor exposure and dampness, however, appears to be associated with an increased risk of developing asthma in young children and asthma morbidity in individuals who have asthma. These are important issues because they provide a rationale for interventions that might be considered for homes and buildings in which there is increased fungal exposure. In addition to rhinitis and asthma, fungus exposure is associated with a number of other illnesses including allergic bronchopulmonary mycoses, allergic fungal sinusitis, and hypersensitivity pneumonitis. Additional research is necessary to establish causality and evaluate interventions for fungal- and dampness-related health effects.

Innate and Adaptive Immune Response to Fungal Products and Allergens

Exposure to fungi and their products is practically ubiquitous, yet most of this is of little consequence to most healthy individuals. This is because there are a number of elaborate mechanisms to deal with these exposures. Most of these mechanisms are designed to recognize and neutralize such exposures. However, in understanding these mechanisms it has become clear that many of them overlap with our ability to respond to disruptions in tissue function caused by trauma or deterioration. These responses involve the innate and adaptive immune systems usually through the activation of nuclear factor kappa B and the production of cytokines that are considered inflammatory accompanied by other factors that can moderate these reactivities. Depending on different genetic backgrounds and the extent of activation of these mechanisms, various pathologies with resulting symptoms can ensue. Complicating this is the fact that these mechanisms can bias toward type 2 innate and adaptive immune responses. Thus, to understand what we refer to as allergens from fungal sources, we must first understand how they influence these innate mechanisms. In doing so it has become clear that many of the proteins that are described as fungal allergens are essentially homologues of our own proteins that signal or cause tissue disruptions.

Procedures to Assist Health Care Providers to Determine When Home Assessments for Potential Mold Exposure Are Warranted.

Drawing evidence from epidemiology and exposure assessment studies and recommendations from expert practice, we describe a process to guide health care providers helping their patients who present with symptoms that might be associated with living in damp housing. We present the procedures in the form of a guided 2-part interview. The first part has 5 questions that triage the patient toward a more detailed questionnaire that reflects features of housing conditions known to be reliably associated with exposures to mold and dampness contaminants. We chose the questions based on the conditions associated with moisture problems in homes across the United States and Canada. The goal is to facilitate the clinicians effort to help patients reduce exposure to environmental triggers that elicit symptoms to better manage their disease.

Home Assessment and Remediation

Awareness of the relationship of fungi to asthma in indoor air is very old and well documented. There is substantial evidence that mold and dampness exacerbate asthma in sensitized individuals. Many governmental and nongovernmental organizations around the world have issued guidelines to the effect that the elimination of moisture intrusion and the removal of moldy items from living space can improve respiratory health. The process of home assessment for moisture and mold presence is discussed along with factors that can be used to guide fungal exposure reduction efforts. An approach to the assessment process itself is outlined, and common causes of moisture and mold damage are described. Points that should be included in a report resulting from a home assessment and rudimentary elements of report interpretation are discussed. Emphasis is that interpretation of sampling for moisture and fungal presence should be provided by the person performing the assessment. We conclude that multifaceted remediation contributes to fungal allergen avoidance. The use of an indoor environmental professional to generate evaluation reports and remediation activities can be a valuable contribution to an overall allergen avoidance strategy.