Chest Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brooks, S. M.
Right arrow Articles by McCluskey, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brooks, S. M.
Right arrow Articles by McCluskey, J. D.
(Chest. 2005;128:1720-1727.)
© 2005 American College of Chest Physicians

The Spectrum of Building-Related Airway Disorders*

Difficulty in Retrospectively Diagnosing Building-Related Asthma

Stuart M. Brooks, MD; Wil Spaul, PhD and James D. McCluskey, MD

* From the Department of Environmental and Occupational Health (Drs. Spaul and Brooks), College of Public Health, and Department of Internal Medicine (Drs. Brooks and McCluskey), College Of Medicine, University of South Florida, Tampa, FL.

Correspondence to: Stuart M. Brooks, MD, University of South Florida, College of Public Health, 13201 Bruce B. Downs Blvd, MDC 56, Tampa, FL 33612; e-mail: sbrooks{at}hsc.usf.edu


   Abstract
TOP
 Abstract
Introduction
 Methods and Materials
 Results
 Discussion
 Conclusion
 References
 
Introduction: The specific causes and mechanism(s) for asthma occurring among occupants of nonresidential buildings with poor indoor air quality are not known, but allergic and nonallergic processes are possible explanations

Methods: Repeated indoor air quality measurements were made while employees were working in a building where cigarette smoking was allowed. Seven of 19 employees who sought medical care from their private physicians because of respiratory complaints received a diagnosis of asthma. Subsequently, 19 symptomatic employees were examined at the University of South Florida (USF) 2 ± 0.8 months (mean ± SD) after removal from the building.

Results: The first floor of the building, where employee complaints were prevalent, was characterized by markedly reduced outdoor fresh air supply, diminished air circulation to the occupant spaces, and elevated airborne concentrations of formaldehyde. Nineteen workers examined at the USF 2 ± 0.8 months after leaving the building reported ear, nose, and throat irritation and asthma-like symptoms while working in the building. There was resolution of symptoms in most of the seven employees (37%) with asthma previously diagnosed by their private physician. In fact, 16 of 19 subjects (84%) reported resolution or significant improvement of symptoms. Among 11 persons with symptoms suggesting asthma while working in the building, 4 persons (21%) showed a negative provocative concentration of methacholine producing a 20% fall in FEV1, including two subjects with doctor-diagnosed asthma.

Conclusions: Confirmation of building-related asthma is influenced by time factors and the clinical criteria used for diagnosis. A nonallergic mechanism seems operative in our cases. While considered an example of occupational asthma, building-related asthma is a challenge for the practicing physician to confirm retrospectively.

Key Words: building-related asthma • environmental tobacco smoke • formaldehyde • indoor air quality • irritant-induced asthma


   Introduction
TOP
 Abstract
 Introduction
Methods and Materials
 Results
 Discussion
 Conclusion
 References
 
The specific cause and mechanism responsible for asthma occurring among occupants of nonresidential buildings with poor indoor air quality are not known, but allergic and nonallergic processes are possible explanations.123 Dust mite, pet, and cockroach allergens are usually associated with the home environment.3 Mold has the potential for producing allergic responses at nonresidential sites.4 Volatile organic compounds, formaldehyde, and reactive chemicals are potential causative agents for a nonallergic, nonresidential etiology.45

This report describes employees working on the first floor of a nonresidential building with adverse indoor air quality typified by reduced delivery of fresh air from the outdoors and elevated levels of formaldehyde and possibly other irritant vapors. Many of the individuals became ill, and some sought medical care because of new-onset asthma. Subsequently, these employees were evaluated approximately 2 months after their exposure in the building was terminated. The results of the investigation suggest that a clinical designation of building-related asthma requires caution and underscores the difficulty a practicing physician may have in retrospectively reaching such as diagnosis.


   Methods and Materials
TOP
 Abstract
 Introduction
 Methods and Materials
Results
 Discussion
 Conclusion
 References
 
Details of the Building
The first floor of a two-story building serviced customers who entered and exited the building on a continuous basis, while the second floor was used as office space, a conference room, and a break room. Cigarette smoking was permitted on both floors without restriction. The health complaints started shortly after a contractor completed repairs on a first-floor heating, ventilation, and air-conditioning (HVAC) unit; there were separate HVAC systems for each floor. Over the next few months, employees on the first floor reported respiratory and mucosal irritation-type symptoms and noted an odor, most often described as a "dead fish smell." Some symptomatic workers consulted their private physician, and some received a diagnosis of "asthma." Within 2 years of occupancy, all employees were removed from the facility to another location as result of health concerns and employee dissatisfaction with these spaces. Symptomatic employees were subsequently evaluated at the University of South Florida (USF) within 1 to 4 months after vacating the building

Indoor Air Quality Measurements
Repeated environmental measurements were completed on both floors over a several-month period while employees were still working in the building; concurrent outdoor measurements were also completed. Ventilation measurements utilized standardized methods to determine ventilation rates for each floor in cubic feet per minute (CFM).6 The percentage of outdoor air that was added to the indoor ventilation was calculated from corrected airflow measurements from an (Alnor flow head products; Shoreview, MN) , rotating vane anemometer and a heated element anemometer.7 Air sampling for formaldehyde, conducted over a 6- to 8-h sampling period, used a portable sampling pump calibrated to 1 L/min and a pair of in-line midget impingers containing a sodium bisulfate media. Samples were analyzed by spectrophotometry using an analytical method with a detection limit of approximately 0.001 ppm for an 8-h sample. Airborne bioaerosols were sampled using the Anderson N6 method with malt extract in agar.6

Examination at the USF
The USF evaluations took place 2 ± 0.8 months (mean ± SD; range, 1 to 4 months) after subjects were removed from the building and had no further building-related exposures. The USF examinations included completion of a questionnaire, directed medical and allergic history, physical examination, allergy skin-prick tests, spirometry, and methacholine challenge. Subjects were asked whether they sought medical care and received a doctor’s diagnosis and/or treatment of asthma during the time they were working in the building. Questioning also addressed "bronchial irritability" to a variety of exposures such as cigarette smoke, aerosol sprays, strong odors, and other nonspecific triggers.8 USF testing adhered to accepted guidelines for spirometry and methacholine challenge testing.91011 For the latter, increasing concentrations of methacholine from 0.03 to 32 mg/mL were aerosolized using a Wright nebulizer (S&M Instruments; Doylestown, PA) that was driven by compressed air. A positive response was determined by extrapolation of the doses to where there was a ≥ 20% fall in FEV1 (provocative concentration of methacholine causing a 20% fall in FEV1 [PC20]). Allergy skin-prick testing was performed and interpreted in a standard way to 55 different allergens including 17 types of mold allergens. A positive skin-prick test result required erythema > 21 mm in diameter and a wheal ≥ 3 mm (eg, 2 + skin test). If skin-prick test results were negative or equivocal, intradermal testing was used at a concentration of 1:500.

Clinical designations were based on the symptoms subjects reported having during the time they were working. A designation of upper airway irritation required reporting two or more eye, nose, and/or throat symptoms considered indicative of irritation (eyes: eyes itching, tearing, burning, eyelid swelling, light sensitivity or eye pain; nose: nasal burning or repeated sneezing, runny, or stuffy nose; throat: sore throat). Employees considered to have asthma symptoms complex claimed a "yes" response to three or more typical asthma symptoms during their employment in the building.12 The typical asthma symptoms were as follows: (1) episodic cough with or without sputum production, (2) self-evident wheezing, (3) exertional and/or episodic shortness of breath, and (4) chest tightness associated with breathlessness.12 A doctor’s diagnosis of asthma implied a diagnosis of asthma made by a private physician during employment in the building and before the USF evaluation; this fact was documented by both subject statement and review of the medical records. The doctor’s treatment for asthma was also documented by both subject statement and review of the medical records.


   Results
TOP
 Abstract
 Introduction
 Methods and Materials
 Results
Discussion
 Conclusion
 References
 
Environmental Data
Table 1 reports the first and second floors and outdoor environmental measurements while subjects were still working. A decreased delivery of fresh air from the outdoors to the first floor was significantly reduced to 3.6% (approximately 0.012 L/s/feet2). The value of 6.7 CFM of total outdoor fresh airflow rate per individual was approximately one third of the recommended value and based on occupancy of 21 employees.13 This reduced value is considered an overestimation since the first floor constantly serviced customers, and typically > 21 people were present indoors. Additionally, carbon dioxide concentrations on the first floor, an indirect measurement of the adequacy of fresh outdoor airflow, were significantly elevated. Table 1 also provides an estimated level of comfort.14 Delivery of air to the second floor was considered adequate. There was 7 to 9% outside air delivery and 11.5 to 46 CFM per individual based on the variation in numbers of employees present throughout the day. There was also diminished air circulation to the occupant spaces because a six-foot section of damaged duct had been removed by a contractor but the new replacement ductwork was never reconnected (Fig 1 , top, A); this led to a major short circuiting of the supply air to the above ceiling return plenum and a circulating ventilation of only 65% of design specifications to the occupants of the first floor. A visual inspection of the ventilation coils of one of the HVAC units revealed excessive mold and bacterial slime growths (Fig 1, bottom, B). A "fishy" odor noted in the immediate area surrounding this HVAC unit was very pronounced inside this unit at the coils. Formaldehyde concentrations on the first floor were approximately 10 to 20 times higher than the measurements recorded on the second floor (Table 1). Formaldehyde levels in individual offices, where smoking occurred, were even higher and averaged 1,180 ± 420 µg/m3 (n = 4). The concentrations of airborne viable fungi on both floors were similar; outdoors samples were approximately three times higher than indoor concentrations. There were no differences in indoor viable fungi concentrations with the HVAC system operating or turned off. Growths of Aspergillus, Penicillium, Cladosporium, Alternaria, Rhizopus, Scopulariopus, Verticillium, and Paecilomyce were cultured on both indoor and outdoor samples.


View this table:
[in this window]
[in a new window]

  		Table 1.. Environmental Measurements

 


View larger version (109K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1.. Environmental measurements revealed reduced HVAC ventilation rates and insufficient outdoor fresh air ventilation. This situation resulted in the buildup of indoor pollutants. The circumstance was in part due to a disconnected ventilation duct to the first floor and blockage of the outdoor air inlet. Top, A: Disconnected ventilation duct (arrow). Bottom, B: Cooling coils contaminated with mold growth.

 
Study Participants
The final study population (19 symptomatic first-floor employees) was identified after an initial telephone survey documented that 21 of 46 employees (46%) reported the onset of respiratory symptoms while working in the building. Among the 21 employees claiming onset of symptoms while working in the building, 19 persons worked on the first floor and 2 persons worked in offices on the second floor. The two symptomatic workers from the second floor refused to participate in any further investigations. The 25 employees who denied having respiratory symptoms were excluded from further investigations. Two of the asymptomatic employees were located on the first floor and 23 worked on the second floor.

The mainly female study population of 19 subjects (18 women and 1 man) had an age range of 18 to 56 years (median, 44 years). Spirometry findings of one current cigarette smoker (20 pack-years) showed an FEV1 of 66% predicted. This individual did not report asthma symptoms, did not have an asthma diagnosis, and showed a negative methacholine challenge test result (PC20 ≥ 16 mg/mL). Two former cigarette smokers (> 10-year cessation) and the remaining 16 subjects were nonsmokers. By the time of the USF evaluation (2 ± 0.8 months; range, 1 to 4 months after leaving the building), 16 of 19 employees (84%) reported significant improvement or resolution of their symptoms. Three subjects reported only minor improvement since vacating the building.

Airway Symptoms
All subjects claimed onset of respiratory symptoms after the ductwork was supposedly repaired. Upper airway irritation symptoms were reported by all 19 subjects while they were working in the building. A breakdown showed 14 persons (74%) each with eye complaints and/or nasal symptoms; sinus-type symptoms were described by 7 employees (37%). Repeated "cold symptoms" were noted by 8 subjects (42%), while an odor was noticed by 12 subjects (63%). Additionally, seven persons (37%) recalled the occurrence of voice changes or repeated headaches. Twelve subjects (63%) fulfilled the criteria for asthma symptoms complex. Itemization of the individual asthma symptoms showed 16 subjects (84%) reported having the sensation of chest tightness associated with breathlessness; 15 subjects (79%) described shortness of breath with exertion; 4 persons (21%) noted intermittent wheezing; and, 11 subjects (74%) described episodic cough. In addition, nocturnal complaints and bronchial irritability were noted in five subjects (26%) and seven subjects (37%), respectively. One person claimed a history of asthma that was in remission for > 1 year. Nonspecific symptoms reported were as follows: fatigue (79%), difficulty in concentrating (37%), problems sleeping (26%), sensation of panic (21%), a feeling of being nervous (16%) or irritable (10%), and unsteady gait (10%). There were 12 subjects (63%) suffering from headaches.

Doctor’s Diagnosis of Asthma
Seven of 19 persons (37%) purported building-related asthma because they acquired new-onset asthma symptoms during their employment in the building, sought medical care, and received a diagnosis of asthma and were treated for asthma by a physician. Six of seven subjects with doctor-diagnosed asthma reported a resolution of asthma symptoms after leaving the building; the other patients was markedly improved. The time period from cessation of building exposure to the USF evaluation was 6.8 ± 1.9 weeks for doctor-diagnosed asthma subjects and 8.8 ± 4.3 weeks for those without a diagnosis of asthma. Table 2 notes that the doctor-diagnosed asthma group was younger (p < 0.05) and more often reported a family history of allergies than subjects who did not receive this designation. Perusal of medical records of the seven doctor-diagnosed asthma cases documented pre-USF spirometric variability in FEV1 (≥ 10%) and/or a significant inhaled bronchodilator response (≥ 12%) in two subjects. One subject with doctor-diagnosed asthma imparted a history suggestive of childhood asthma, but there were infrequent attacks of "bronchitis" during adulthood and no acute attacks for > 1 year. Persons not considered to have doctor-diagnosed asthma showed a similar prevalence of asthma symptom complex, a similar extent of allergy skin-prick test reactivity, but a somewhat higher mold skin test reactivity. Nocturnal attacks and bronchial irritability were noted in both groups.


View this table:
[in this window]
[in a new window]

  		Table 2.. Comparisons Between Doctor-Diagnosed Asthma Cases and Cases Without Doctor-Diagnosed Asthma at the Time of the USF Evaluation*

 
Methacholine Reactivity
Table 3 categorizes subjects into three groups according to PC20 values: group 1 (n = 5) had positive results, with PC20 values ≤ 8 mg/mL; group 2 (n = 6) had indeterminate results, with PC20 values > 8 to ≤ 16 mg/mL; and group 3 (n = 8) had negative results, with PC20 ≥ 16 mg/mL. The three groups were similar for numbers, age, and FEV1 percentage of predicted, as well as for personal and family history of allergy and skin-prick test reactivity. Cough and wheezing were more frequent in the PC20-positive and PC20-intermediate groups. Of 11 subjects (58%) who fulfilled the asthma symptom complex criteria, 4 persons (21%) had a negative PC20 findings.


View this table:
[in this window]
[in a new window]

  		Table 3.. Subjects Categorized According to PC20 Value*

 

   Discussion
TOP
 Abstract
 Introduction
 Methods and Materials
 Results
 Discussion
Conclusion
 References
 
Irritation symptoms and asthma-like complaints were described by persons working in a building complicated by markedly reduced outdoor fresh air supply, diminished air circulation to the occupant spaces, and elevated airborne concentrations of formaldehyde. Seven of these individuals (37%) sought medical care and received a diagnosis of asthma and were treated by their private physician. The distinctiveness of the building environment is important to emphasize because indoor pollutants tend to build up when ventilation rates are low and respiratory and irritation symptoms become more prevalent in buildings where smoking is permitted and the outdoor air supply is < 20 CFM per person.1314 We believe the irritation and airway complaints can be linked to the reduced outdoor air supply and elevated airborne concentrations of irritant vapors, specifically formaldehyde.1415 The airborne formaldehyde concentrations on the first floor were 10 to 20 times higher than the second-floor concentrations, and > 80 times higher than outdoor concentrations. The first floor formaldehyde measurements of 170 to 570 µg/m3 are consistent with reports of eye irritation symptoms developing at levels as low as 10 µg/m3 and throat irritation complaints occurring in the range of 120 to 3,000 µg/m3 formaldehyde concentrations.16 Data for buildings where occupants report irritation-type symptoms showed a range of formaldehyde concentration of 140 to 1,920 µg/m3.17 Elevated formaldehyde concentrations have been associated with irritation symptoms and development of asthma-like symptoms.518 The first-floor concentrations approximate formaldehyde concentrations reported for mobile homes, where urea formaldehyde resins have been used, and where concentrations of 240 to 610 µg/m3 are often found.5 People in mobile homes with these concentrations of formaldehyde may describe irritation and asthma-like symptoms. The first-floor formaldehyde concentrations exceeded the Swedish limit value for dwellings (100 µg/m3).19 In contrast, the second-floor formaldehyde concentrations (18 to 60 µg/m3), where respiratory complaints did not generally occur, more closely simulated conventional homes (37 to 110 µg/m3) and nonproblem commercial office buildings (1.7 to 13.3 µg/m3).51920

Our findings of higher levels of formaldehyde in individual offices where smoking occurred (often > 1,000 µg/m3) suggest that a primary source of formaldehyde emissions was due to cigarette smoke as opposed to a building-related product or process. We believe that environmental tobacco smoke likely played an important role in the irritation complaints.21 Caution must be exercised when claiming subjects’ airway complaints are secondary to formaldehyde, since human studies1618 suggest that much higher levels of formaldehyde than that measured in our study are required to produce airway responses. Airborne formaldehyde concentrations might have been a surrogate for reduced outdoor air supply, much like the way carbon dioxide concentrations are used in occupied buildings. Indoor irritants can react with one another (or themselves) to create reactive oxygen species, which are important in promoting airway inflammation, a finding characteristic of asthma.2223

Through our direct observation and inspection, we discovered moisture, a dead fish-like odor, and the presence of mold, water stains, and indications of leaks and flooding. Damp conditions have been associated with physician-diagnosed asthma and with the presence of asthmatic-type symptoms.124 Mold have been implicated in building-related asthma.1421 However, when repeatedly measured, airborne viable mold concentrations were much lower on the first floor than concentrations measured outdoors, which would support the argument that mold spores were not being released inside this building at a significant rate.

Seven workers sought medical care from their private physician and received a diagnosis of asthma and treatment for asthma. We believe these individuals can be considered to have building-related asthma. An observation worthy of note was the relatively rapid resolution of asthma symptoms following cessation of the indoor exposure. By the time of the USF examination some 2 months after vacating the building, 16 of 19 persons (84%) reported improvement or resolution of their symptoms, while 3 subjects reported only minor improvement. This finding contrasts to typical allergic-type occupational asthma in which symptoms may persist for years after cessation of exposure.2526 The rapid resolution of asthma symptoms related to poor indoor air quality holds significance because this phenomenon might make it more difficult to retrospectively confirm a diagnosis of building-related asthma. Persons examined weeks or months after vacating a building may undergo rapid clinical transformation. This hypothesis has substance, since we found that the reporting of three or more asthma symptoms (while working in the building) did not sufficiently differentiate doctor-diagnosed asthma from non–doctor-diagnosed asthma cases, a finding similar to other investigations.827

A diagnosis of building-related asthma is more problematic when nonallergic causes are considered, especially when the exact constituents of the irritant exposure are not well defined. Asthma symptoms can be transient when an irritant is the offending agent and treatment has been instituted.28 While there are specific criteria for the diagnosis of reactive airways dysfunction syndrome from a high-level irritant exposure,29 irritant-induced asthma from a lower-level irritant exposure is more difficult to conclude. Some of the difficulty in reaching a definitive diagnosis of building-related asthma may also relate to the complex definition of asthma.30 The present investigation suggests that in building-related asthma, various physiologic and clinical features typical of this definition may be absent at a time after subjects leave the building. Possibly there is dissociation between airway inflammation and airway hyperresponsiveness.31 Airway inflammation resolves slower than clinical manifestations and airway hyperresponsiveness.32

Methacholine reactivity has been used to denote the presence of asthma.82627 Two of the doctor-diagnosed asthma subjects had PC20 values ≥ 16 mg/mL. There are several possible explanations for the absence of airway hyperresponsiveness in persons with doctor-diagnosed asthma under the scenario of this investigation. Subjects were evaluated on average of 2 months after leaving the building and reported resolution or subjective improvement in their symptoms. The short duration of exposure and perhaps the absence of persistent airway remodeling are influential in the resolving airway hyperresponsiveness.33 Reversal of methacholine reactivity can be rapid, and PC20 can normalize as soon as 2 to 3 h after an inhalation of a sensitizing agent.34 Occupational asthma can be present without bronchial hyperresponsiveness.35 Asthmatic symptoms are reported in subjects whose methacholine challenge test results are negative.363738 The sensitivity of methacholine reactivity for confirming cases of occupational asthma is only approximately 50%.39 As many as one third of asymptomatic persons in the general population demonstrate a positive methacholine challenge test finding,40 and approximately 10% of workers with no respiratory symptoms show PC20 values ≤ 8 mg/mL.27

We relied on the designation of doctor-diagnosed asthma, which is said to be highly specific for identifying asthmatics.4142 A doctor’s diagnosis of asthma is readily used in epidemiologic studies273843 to identify cases of asthma, but its designation may not be precise for the individual cases we investigated. Our group with doctor-diagnosed asthma was younger and more often reported a family history of allergy than the group without doctor-diagnosed asthma. The significance of this difference is not known.

The clinical characteristics of our subjects resemble the office worker reported by Hoffman et al.2 This individual showed work-related significant fall in peak expiratory flow and recovery within 1 h after leaving the building. Methacholine reactivity improved within 2 to 3 months of leaving the building. In addition, the clinical presentation and course of our subjects is similar to individuals reported with noneosinophilic occupational asthma.44 Some of the reported causative agents for noneosinophilic occupational asthma, such as burning-plastics, floor cleaner, welding fumes, and formaldehyde, are more accurately characterized as irritants. Our data supports a nonallergic mechanism for the airway complaints described by the subjects we investigated. Whether our cases represent examples of noneosinophilic asthma is conjectural.


   Conclusion
TOP
 Abstract
 Introduction
 Methods and Materials
 Results
 Discussion
 Conclusion
References
 
Employees worked on the first floor of a nonresidential building with adverse indoor air quality that was typified by reduced delivery of fresh air from the outdoors and elevated levels of formaldehyde. Many of the individuals became ill and some sought medical care because of new-onset asthma. Subsequently, these employees were evaluated approximately 2 months after their exposure in the building was terminated. The results of the investigation suggest that a clinical designation of building-related asthma requires caution and underscores the difficulty a practicing physician may have in retrospectively reaching such as diagnosis.


   Acknowledgements
 
We thank Dr. Roger Fox for performing allergy skin testing and Drs. Marcel Targino and Pedro M. Ojeda for data collection.


   Footnotes
 
Abbreviations: CFM = cubic feet per minute; HVAC = heating, ventilation, and air-conditioning; PC20 = provocative concentration of methacholine producing a 20% fall in FEV1; USF = University of South Florida

This work was performed at the University of South Florida, College of Public Health.

Received for publication October 7, 2004. Accepted for publication March 14, 2005.


   References
TOP
 Abstract
 Introduction
 Methods and Materials
 Results
 Discussion
 Conclusion
 References
 

  1. . Institute of Medicine, Committee on Damp Indoor Spaces and Health, Board on Health Promotion and Disease Prevention. (2004) Damp indoor spaces and health. National Academy Press. Washington, DC:
  2. Hoffman, RE, Wood, RC, Kreiss, K Building-related asthma in Denver office workers. Am J Public Health 1993;83,89-93[Abstract/Free Full Text]
  3. Institute of Medicine, Committee on the Assessment of Asthma and Indoor Air, Division of Health Promotion and Disease Prevention.. Asthma and nonresidential indoor environments. Clearing the air: asthma and indoor exposures. 2000,316-326 National Academy Press. Washington, DC:
  4. Ross, MA, Curtis, L, Scheff, PA, et al Association of asthma symptoms and severity with indoor bioaerosols. Allergy 2000;55,705-711[CrossRef][ISI][Medline]
  5. Wieslander, G, Norback, D, Bjornsson, E, et al Asthma and the indoor environment: the significance of emission of formaldehyde and volatile organic compounds from newly painted indoor surfaces. Int Arch Occup Environ Health 1997;69,115-124[CrossRef][ISI][Medline]
  6. National Institute for Occupational Safety and Health.. NIOSH manual of analytical methods 1986 National Institute for Occupational Safety and Health. Cincinnati, OH:
  7. Clayton, GD, associates.. Design of ventilation systems. US Department of Health Education and Welfare CDC, NIOSH, ed. The industrial environment: its evaluation and control. 1973,609-628 US Government Printing Office. Washington, DC:
  8. Brooks, SM The evaluation of occupational airways disease in the laboratory and workplace. J Allergy Clin Immunol 1982;70,56-66[Medline]
  9. American Thoracic Society.. Standardization of spirometry: 1987 update; ATS statement. Am Rev Respir Dis 1987;136,1285-1298[ISI][Medline]
  10. American Thoracic Society.. Lung function testing: selection of reference values and interpretative strategies; ATS statement. Am Rev Respir Dis 1991;144,1202-1218[ISI][Medline]
  11. Cockcroft, DW, Killian, DN, Mellon, JJ, et al Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy 1977;71,235-243
  12. Brooks, SM, Bernstein, IL, Raghuprasad, PK, et al Assessment of airway hyperresponsiveness in chronic stable asthma. J Allergy Clin Immunol 1990;85,17-26[CrossRef][ISI][Medline]
  13. ASHRAE Standard 62–1999: ventilation for acceptable indoor air quality. 1999 American Society of Heating, Refrigerating, and Air-Conditioning Engineers. Atlanta, GA:
  14. Menzies, D, Bourbeau, J Building-related illnesses. N Engl J Med 1997;337,1524-1531[Free Full Text]
  15. Norback, D, Walinder, R, Wieslander, G, et al Indoor air pollutants in schools: nasal patency and biomarkers in nasal lavage. Allergy 2000;55,163-170[CrossRef][ISI][Medline]
  16. Harrison, PTC Indoor air pollution. D’Amato, G Holgate, ST eds. The impact of air pollution on respiratory health 2002,117-132 Charlesworth Group. Huddersfield, UK:
  17. Main, DM, Hogan, TJ Health effects of low-level exposure to formaldehyde. J Occup Med 1983;25,896-900[CrossRef][ISI][Medline]
  18. Krakowiak, A, Gorski, P, Pazdrak, K, et al Airway response to formaldehyde inhalation in asthmatic subjects with suspected respiratory formaldehyde sensitization. Am J Ind Med 1998;33,274-281[Medline]
  19. Norback, D, Bjornsson, E, Janson, C, et al Asthmatic symptoms and volatile organic compounds, formaldehyde, and carbon dioxide in dwellings. Occup Environ Med 1995;52,388-395[Abstract]
  20. Reynolds, SJ, Black, DW, Borin, SS, et al Indoor environmental quality in six commercial office buildings in the Midwest United States. Appl Occup Environ Hyg 2001;16,1065-1077[CrossRef][Medline]
  21. Thorn, J, Brisman, J, Toren, K Adult-onset asthma is associated with self-reported mold or environmental tobacco smoke exposures in the home. Allergy 2001;56,287-292[CrossRef][ISI][Medline]
  22. Wolkoff, P, Clausen, PA, Wilkins, CK, et al Formation of strong airway irritants in terpene/ozone mixtures. Indoor Air 2000;10,82-91[CrossRef][ISI][Medline]
  23. Li, TH, Turpin, BJ, Shields, HC, et al Indoor hydrogen peroxide derived from ozone/d-limonene reactions. Environ Sci Technol 2002;36,3295-3302[Medline]
  24. Institute of Medicine, Committee on the Assessment of Asthma and Indoor Air, Division of Health Promotion and Disease Prevention.. Asthma and nonresidential indoor environments. Clearing the air: asthma and indoor exposures. 2000,298-315 National Academy Press. Washington, DC:
  25. Lemiere, C, Cartier, A, Dolovich, J, et al Outcome of specific bronchial responsiveness to occupational agents after removal from exposure. Am J Respir Crit Care Med 1996;154,329-333[Abstract]
  26. Malo, JL, Ghezzo, H Recovery of methacholine responsiveness after end of exposure in occupational asthma. Am J Respir Crit Care Med 2004;169,1304-1307[Abstract/Free Full Text]
  27. Enarson, DA, Vedal, S, Schulzer, M, et al Asthma, asthma-like symptoms, chronic bronchitis, and the degree of bronchial hyperresponsiveness in epidemiologic surveys. Am Rev Respir Dis 1987;136,613-617[ISI][Medline]
  28. Lemiere, C, Malo, JL, Boutet, M Reactive airways dysfunction syndrome due to chlorine: sequential bronchial biopsies and functional assessment. Eur Respir J 1997;10,241-244[Abstract]
  29. Brooks, SM, Weiss, MA, Bernstein, IL Reactive airways dysfunction syndrome (RADS): persistent asthma syndrome after high level irritant exposure. Chest 1985;88,376-384[Abstract/Free Full Text]
  30. National Institute of Health.. Guideline for the diagnosis and management of asthma. 1997,1-153 National Heart Lung and Blood Institute. Bethesda, MD:
  31. Crimi, E, Spanevello, A, Neri, M, et al Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med 1998;157,4-9
  32. Maghni, K, Lemiere, C, Ghezzo, H, et al Airway inflammation after cessation of exposure to agents causing occupational asthma. Am J Respir Crit Care Med 2004;169,367-372[Abstract/Free Full Text]
  33. Beckett, PA, Howarth, PH Pharmacotherapy and airway remodelling in asthma? Thorax 2003;58,163-174[Abstract/Free Full Text]
  34. Durham, SR, Graneek, BJ, Hawkins, R, et al The temporal relationship between increases in airway responsiveness to histamine and late asthmatic responses induced by occupational agents. J Allergy Clin Immunol 1987;79,398-406[Medline]
  35. Smith, AB, Brooks, SM, Blanchard, J, et al Absence of airway hyperreactivity to methacholine in a worker sensitized to toluene diisocyanate (TDI). J Occup Med 1980;22,327-331[CrossRef][ISI][Medline]
  36. Desjardins, A, de Luca, S, Cartier, A, et al Nonspecific bronchial hyperresponsiveness to inhaled histamine and hyperventilation of cold dry air in subjects with respiratory symptoms of uncertain etiology. Am Rev Respir Dis 1988;137,1020-1025[ISI][Medline]
  37. Pattemore, PK, Asher, MI, Harrison, AC, et al The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms. Am Rev Respir Dis 1990;142,549-554[ISI][Medline]
  38. Dales, RE, Nunes, F, Partyka, D, et al Clinical prediction of airways hyperresponsiveness. Chest 1988;93,984-986[Abstract/Free Full Text]
  39. Baur, X, Huber, H, Degens, PO, et al Relation between occupational asthma case history, bronchial methacholine challenge, and specific challenge test in patients with suspected occupational asthma. Am J Ind Med 1998;33,114-122[CrossRef][ISI][Medline]
  40. Boulet, LP Asymptomatic airway hyperresponsiveness: a curiosity or an opportunity to prevent asthma? Am J Respir Crit Care Med 2003;167,371-378[Free Full Text]
  41. Toren, K, Brisman, J, Jarvholm, B Asthma and asthma-like symptoms in adults assessed by questionnaires: a literature review. Chest 1993;104,600-608[Abstract/Free Full Text]
  42. Johnson, AR, Dimich-Ward, HD, Manfreda, J, et al Occupational asthma in adults in six Canadian Communities. Am J Respir Crit Care Med 2000;162,2058-2062[Abstract/Free Full Text]
  43. Adelroth, E, Hargreave, FE, Ramsdale, EH Do physicians need objective measurements to diagnose asthma? Am Rev Respir Dis 1986;134,704-707[ISI][Medline]
  44. Anees, W, Huggins, V, Pavord, ID, et al Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants. Thorax 2002;57,231-236[Abstract/Free Full Text]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brooks, S. M.
Right arrow Articles by McCluskey, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brooks, S. M.
Right arrow Articles by McCluskey, J. D.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS