Evaluation of Respiratory Health 

among Employees in a WaterDamaged Office Building– 

Connecticut 

HETA 2001-0445-3141 

Connecticut 

September 2011 

DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Centers for Disease Control and Prevention 

Workplace

Safety and Health

 National Institute for Occupational 

Safety and Health 

This Health Hazard Evaluation (HHE) report and any recommendations made herein are for the specific 

facility evaluated and may not be universally applicable. Additional HHE reports are available at http:// 

www.cdc.gov/niosh/hhe/ 

Ju-Hyeong Park, ScD

Sandra K. White, MS 

Sook Ja Cho, PhD 

Jean M. Cox-Ganser, PhD 

Health Hazard Evaluation Report
 
The employer shall post a copy of this report 

for a period of 30 calendar days at or near 

the workplace(s) of affected employees. The 

employer shall take steps to insure that the 

posted determinations are not altered, defaced, or 

covered by other material during such period. [37 

FR 23640, November 7, 1972, as amended at 45 

FR 2653, January 14, 1980]. 
Contents
 

RepoRt
 Abbreviations .................................................................................. ii
 

Highlights of the NIOSH Health Hazard Evaluation................... iii
 

Summary..........................................................................................6
 

Introduction .....................................................................................8
 

Methods .........................................................................................10
 

Results............................................................................................24
 

Discussion......................................................................................53
 

Conclusions....................................................................................58
 

Recommendations.........................................................................59
 

References......................................................................................60
 

ACknowledgments Acknowledgements and Availability of Report .............................63
 

Health Hazard Evaluation Report 2001-0445-3141 Page i 
AbbReviAtions
 

μg Micrograms 

Aw Water activity 

BR Building-related 

CFU Colony forming units 

CI Confidence interval 

EU Endotoxin units 

FEV1 Forced expiratory volume in the 1st second of exhalation 

FVC Forced vital capacity 

GM Geometric mean 

GSD Geometric standard deviation 

g Gram 

IL-8 Interleukin-8 

IQR Interquartile range 

Ln Natural logarithm 

m2 Meter squared 

mg Milligram 

mg/mL Milligrams per milliliter 

mL Milliliter 

ng Nanogram 

NIOSH National Institute for Occupational Safety and Health 

OR Odds ratio 

PC20 Provocative concentration causing a 20% fall in FEV1 

SD Standard deviation 

Page ii Health Hazard Evaluation Report 2001-0445-3141 
HigHligHts of tHe What NIOSH Did niosH HeAltH 

HAzARd evAluAtion
 

The National Institute 

for Occupational Safety 

and Health (NIOSH) 

received a union request 

for a health hazard 

evaluation at a state office 

building in Connecticut 

because of ongoing 

problems with water 

intrusion. The occupants 

were concerned about 

respiratory symptoms, 

asthma, hypersensitivity 

pneumonitis, and 

sarcoidosis in association 

with the building. Exposure 

to dampness and mold 

in indoor environments 

is a known public health 

hazard. 

●	 NIOSH investigators visited the facility in July 2001 for an 

initial tour of the building. 

●	 We offered health questionnaire surveys to all employees in 

2001, 2004, 2005, and 2007. 

●	 We provided the following medical tests in 2002, 2004, and 

2005 to selected groups of employees: 

o	 Spirometry (breathing tests) 

o	 Methacholine challenge testing or bronchodilator 

testing for asthma 

o	 Skin allergy testing 

o	 Exhaled breath condensate to test for signs of 

inflammation (2002) 

o	 Exhaled nitric oxide (for allergic asthma) (2002) 

o	 Nasal nitric oxide (for nasal allergy) (2005) 

o	 Nasal lavage to test for signs of inflammation (2005) 

●	 We conducted environmental surveys in 2002, 2004, 2005, 

and 2007 and analyzed dust samples, including: 

o	 Culturable mold 

o	 Culturable bacteria 

o	 Endotoxin (a component of cell walls of some 

bacteria) 

o	 Ergosterol (a component of cell walls of mold) 

o	 Glucan (a component of cell walls of mold) 

o	 Actinomycetes (a bacteria sometimes associated with 

allergic lung disease) 

o	 Dog and cat allergens 

What NIOSH Found 

●	 Employees had at least twice the rate of chest symptoms and 

asthma compared to the U.S. population. 

●	 Employees were 7.5 times more likely to develop asthma after 

starting to work in the building compared to their asthma 

risk before they worked in the building. 

●	 Employees with higher exposure to mold or endotoxin had 

higher risk of respiratory symptoms or physician-diagnosed 

post-occupancy asthma compared to those with lower 

exposure within the building. 

Health Hazard Evaluation Report 2001-0445-3141 Page iii
 

 

HigHligHts of tHe 

niosH HeAltH 

HAzARd evAlution 

(Continued) 

●	 Employees starting to work in the building after completion 

of major remediation (January 2004 or later) were less likely 

to report symptoms while employees starting to work in 

the building before completion of major remediation were 

persistently more likely to report symptoms. 

●	 Employees who had medical tests in both 2002 and 2005 did 

not show overall improvement in respiratory health. 

●	 There was an increased risk of developing building-related 

asthma symptoms in any one of the later (2004, 2005, and 

2007) surveys among those who reported building-related 

nasal or sinus symptoms in the 2001 survey compared to 

those who did not report building-related nasal or sinus 

symptoms. 

●	 There were lower microbial levels in 2004 and 2005 

compared to 2002 following major remediation, but higher 

levels in 2007. 

●	 There was a lower proportion of hydrophilic (water-loving) 

fungi among all fungi following remediation in 2004, but 

the proportion increased in 2005 and 2007, consistent with 

recurrent water incursion. 

What Managers Can Do 

●	 Initiate a routine maintenance program for evaluation 

of water damage in the building, including regular 

observational assessment of water stains, mold growth, mold 

odors, and dampness, and systematic evaluation of window 

leaks, roof leaks, and functionality of exterior walls. 

●	 Promptly repair all water incursions once they are identified. 

●	 Ensure proper housekeeping procedures and establish regular 

maintenance schedules. 

●	 Use proper containment measures during water damage 

remediation and building repairs.
 

●	 Keep building occupants updated with information regarding 

environmental and health issues in the building. 

●	 Initiate ongoing medical surveillance for building-related 

disease. 

●	 Relocate occupants with building-related chest and nasal 

symptoms.
 

Page iv	 Health Hazard Evaluation Report 2001-0445-3141 
 

 

HigHligHts of tHe 

niosH HeAltH 

HAzARd evAlution 

(Continued) 

What Employees Can Do 

●	 Promptly report water incursions and other building 

problems to management. 

●	 Report persistent symptoms associated with being in the 

building environment to management and seek medical 

evaluation for diagnosis and management, including 

consideration of restriction from working at implicated 

workstations or in the building. 

Health Hazard Evaluation Report 2001-0445-3141	 Page v 
summARy
 

NIOSH found that 

indices of water damage, 

such as mold and 

endotoxin concentrations 

in vacuumed dust,were 

associated with buildingrelated respiratory 

symptoms and asthma. 

Remediation efforts 

temporarily lowered water 

damage indices but did 

not result in improved 

health in those employees 

already affected. Medical 

surveillance can motivate 

relocation of affected 

employees. Ongoing 

water incursion may be 

partly due to the pre-1987 

building design which did 

not include a continuous 

drainage plane behind the 

brick veneer. 

In July 2001, NIOSH received a health hazard evaluation request 

from a local union representing employees at a state office building 

in Connecticut. There had been reports of asthma, hypersensitivity 

pneumonitis, and sarcoidosis occurring among occupants in the 

building. The building, which had a reported history of water 

incursion and damage, was originally built in 1985 and purchased 

by the state of Connecticut from a private company in 1994. Two 

agencies had been in the office building since the building was 

purchased, with Agency A occupying the 5th, 6th, and upper floors 

(14th–20th) and Agency B on the lower floors (7th–12th floors). In 

2005, another state agency, Agency C, relocated to the 6th floor of 

the building. The first four floors are used for parking. 

NIOSH conducted an initial health survey in 2001 and medical 

and environmental surveys in 2002. After these surveys, the 

building underwent major remediation between 2002 and early 

2004, with additional remediation through 2007. After major 

remediation was completed, NIOSH conducted the first follow-up 

health questionnaire survey in 2004 and two additional followup surveys in 2005 and 2007. NIOSH also performed follow-up 

medical surveys in 2004 and 2005 on a subset of employees, and 

conducted follow-up environmental evaluations in 2004, 2005, 

and 2007. NIOSH invited all occupants to participate in the health 

questionnaire surveys offered in 2001, 2004, 2005, and 2007. 

Results of the 2001 health questionnaire survey indicated elevated 

prevalences of asthma and lower respiratory symptoms in the 

building compared to national and state data. There was a 7.5 

times increased incidence of adult-onset asthma after building 

occupancy compared to before occupancy. Some occupants 

reported new-onset sarcoidosis and hypersensitivity pneumonitis. 

From the initial 2001 health and 2002 environmental surveys, 

NIOSH found that occupants with relatively higher exposure 

to fungi or endotoxin (a cell wall component of Gram-negative 

bacteria) in the building had a greater risk of respiratory symptoms 

and post-occupancy physician-diagnosed asthma in an exposuredependent way, and that occupants with exposure to both 

higher mold and higher endotoxin levels in the building had 

an even greater risk of respiratory illnesses than the summation 

of the individual risks of higher mold and higher endotoxin 

concentrations. 

Throughout the follow-up surveys conducted after the major 

remediation was completed, NIOSH continued to find elevated 

Page 6 Health Hazard Evaluation Report 2001-0445-3141 
summARy (Continued) 

rates of symptoms and disease in the building. Rates of lower 

respiratory symptoms and asthma remained elevated when 

compared to national and state data. However, the new onset 

of diseases such as asthma, hypersensitivity pneumonitis, and 

sarcoidosis appeared to decline after 2001 or 2002. Respiratory 

and non-respiratory complaints were higher among occupants who 

had worked in the building for longer time periods (hired prior to 

2004), compared to occupants with shorter occupancy times (hired 

in 2004 or later). In general, we observed no overall improvement 

in respiratory health, as reflected in symptom scores, overall 

medication use, spirometry abnormalities, or sick leave when we 

compared 97 employees’ paired medical data from 2002 and 2005. 

In addition, occupants who reported building-related nasal or 

sinus symptoms in the 2001 survey had a higher risk of developing 

building-related lower respiratory symptoms (wheeze, chest 

tightness, attacks of shortness of breath, cough, or awakened by 

an attack of breathing difficulty) in any one of the three follow-up 

surveys. In this repeated measurement analysis, data suggest that 

employees with rhinosinusitis symptoms that were not associated 

with building occupancy did not have an increased risk of buildingrelated asthma symptoms. 

The levels of total culturable fungi in the building decreased in 

2004 and 2005 compared to 2002 levels, but increased in 2007. 

This increase in 2007 occurred on all 15 occupied floors and was 

mostly attributable to an increase in hydrophilic fungi (fungal 

group requiring high moisture content to survive and grow on 

substrates). Repeated measurement analysis showed a significant 

effect of remediation in floor dust levels in 2004 and 2005 for 

total and hydrophilic fungi and for endotoxin in 2004, after 

major remediation was completed between 2002 and early 2004. 

However, this remediation effect disappeared in 2007, which 

suggests inadequate ongoing remediation. 

In summary, this office building with a long history of water 

incursion is associated with excess respiratory disease among 

employees. Extensive remediation of water damage temporarily 

lowered indices of microbial contamination but the building 

continued to have recurrent water incursion in 2007 and 2008 

as documented in consultant reports. Although new employees 

occupying the building between 2004 through 2007 had fewer 

respiratory complaints, previously affected employees, on average, 

did not regain their respiratory health. Employees should seek 

medical guidance quickly if they develop symptoms. Ongoing 

medical surveillance can provide health data to guide management 

decisions about relocation of affected employees and risk 

Health Hazard Evaluation Report 2001-0445-3141 Page 7 
summARy (Continued) 

management of continued building occupancy in relation to 

remediation and productivity costs. 

Keywords: NAICS 921130, 922190, 923130 (Public Finance 

Activities; Other Justice, Public Order, and Safety Activities; 

Administration of Human Resource Programs), indoor air pollution, 

indoor air quality, mold, endotoxin, asthma, hypersensitivity 

pneumonitis, sarcoidosis, dampness, water damage 

intRoduCtion	 On July 17, 2001, the National Institute for Occupational 

Safety and Health (NIOSH) received a health hazard evaluation 

request from the Administrative and Residual Employees Union 

representing employees at a state office building in Connecticut. In 

response to this request, NIOSH investigated respiratory diseases 

perceived to be work-related among building occupants. This 

final report presents the findings and recommendations from 

the initial survey in September 2001 and all subsequent medical 

and environmental surveys done by NIOSH at this building from 

April 2002 through August 2007 and will serve to closeout this 

evaluation. 

The building was constructed in 1985 and has been owned and 

managed by the state since 1994. The building houses three state 

agencies: Agency A, Agency B, and Agency C. Agencies A and 

B moved into the building shortly after it was purchased by the 

state, and Agency C moved to the building in 2005. The facility 

is a 20-floor office building with parking garages on the bottom 

four floors and a lobby/cafeteria/mezzanine area on the 5th floor. 

Agency B occupies the lower floors (floors 7–12) while Agency 

A is on the 5th, 6th and upper floors (floors 14–20). Since 2005, 

Agency C employees have also occupied the 6th floor. On average, 

approximately 1,300 people work in the building. 

Since 1994, employees working on the 15 occupied floors of the 

building have reported recurrent water damage and respiratory 

health complaints. The building had problems with water 

incursion through leaks in the roof, around windows, and through 

the sliding doors of terraces on the upper floors. There had been 

plumbing leaks on many floors, which had damaged interior walls. 

The building was found to be operating at negative pressure relative 

to the outdoors, which may have exacerbated water incursion. 

Water damage and mold contamination were worst on the upper 

floors. Some individuals had been diagnosed with post-occupancy 

onset asthma, hypersensitivity pneumonitis, or sarcoidosis and 

had been temporarily relocated to another facility. Hypersensitivity 

Page 8	 Health Hazard Evaluation Report 2001-0445-3141 
intRoduCtion (Continued) 

pneumonitis is a lung disease in which the immune system reacts 

with inhaled microorganisms, forming inflammation or scars called 

granulomas. Cases of the disease sometimes co-exist with cases 

of asthma in damp office buildings. Sarcoidosis is an immunemediated granulomatous multisystem disease of unknown cause. 

Internal and external repairs to the building began prior to the 

health hazard evaluation request in 2001, but major remediation 

was undertaken in 2002 and considered complete by early 2004. 

Additional remediation continued through 2007 as intermittent 

water incursion had occurred after the major remediation. Between 

2000 and 2002, carpets and partitions were cleaned, water-stained 

walls and carpets were replaced, wallpaper and any underlying 

mold in the bathrooms were removed, and high-efficiency filters 

were added to the heating, ventilating, and air conditioning system. 

Major remediation on the building envelope was done between 

2002 and early 2004. By the end of 2003, a 7.5 million dollar 

repair to the exterior of the building had been completed, which 

included repairing the building envelope and replacing the roof 

and sheetrock. An environmental management system to control 

mechanical systems was also added in 2004. Finally, a systematic 

cleaning of all floor surfaces and furnishings was accomplished 

with high-efficiency particulate filter vacuums in early 2004. 

After receiving the health hazard evaluation request in July 2001, 

NIOSH performed an initial health questionnaire survey in 

September 2001, an environmental evaluation in April 2002, 

and medical testing in June 2002. After completion of major 

repairs, NIOSH returned for three follow-up health questionnaire 

and environmental surveys in August 2004, 2005, and 2007. 

Since 2001, NIOSH investigators have provided results, scientific 

findings, and recommendations through 12 interim reports/letters 

to both management and union officials based on observations 

and cross-sectional and repeated measurement analyses on health 

questionnaire, medical, and environmental data. These interim 

reports are available upon request from NIOSH’s Division of 

Respiratory Disease Studies in Morgantown, West Virginia. 

The purposes of this final report are: 1) to summarize and discuss 

the findings from our evaluations during this six-year period 

(2001–2007); 2) to inform how the health status of occupants and 

the building environment changed over this period of time; and 3) 

to examine the impact of remediation in terms of occupant health 

and environmental indices. We also make recommendations 

on assessing the occupants’ ongoing health and monitoring the 

building environment. 

Health Hazard Evaluation Report 2001-0445-3141 Page 9 
metHods 

Health Questionnaire Surveys 

We conducted four cross-sectional health questionnaire surveys 

in 2001, 2004, 2005, and 2007 (Figure 1). To ascertain the health 

status of employees in the building, all persons working in this 

state office building were invited to participate in each of the 

four surveys. In 2007, we also invited current employees who 

had participated in an earlier survey and were now working at 

another location to participate. In the first two surveys (2001 and 

2004), NIOSH staff supervised self-administered paper versions 

of the questionnaire in small groups. In 2005 and 2007, the 

questionnaire was self-administered electronically and run from 

a secure site at the Centers for Disease Control and Prevention 

in Atlanta, Georgia. If employees did not have Internet or e-mail 

access, we mailed each of them a paper copy of the questionnaire. 

All surveys included questions on health symptoms in the last 

12 months and 4 weeks, if the symptoms changed when away 

from the building, medical diagnoses, demographic and smoking 

information, and work history. We defined building-related 

symptoms as those that improved when away from the building. 

Later surveys (2004–2007) included additional questions on the 

number of work days lost due to respiratory and non-respiratory 

problems, perceptions about the building’s environment, and on 

the home environment. In the 2007 questionnaire, we included 

a module on quality of life, which contained questions from the 

SF-12® Health Survey, and questions regarding medication use 

for upper and lower respiratory symptoms. Questions on health 

symptoms and medical diagnoses in the NIOSH questionnaires 

were derived from the American Thoracic Society standardized 

respiratory symptom questionnaire, the 3rd National Health 

and Nutrition Examination Survey, and the Environmental 

Protection Agency Building Assessment Survey and Evaluation 

(questionnaires available upon request). Non-participant surveys 

were done in both 2004 and 2007 to assess responder bias. 

Medical Surveys 

Selection of Invitees for Medical Surveys 

We conducted medical surveys, which included an extended health 

questionnaire and medical testing, in 2002, 2004, and 2005, but 

not in 2007 due to the low participation rate during the 2005 

Page 10 Health Hazard Evaluation Report 2001-0445-3141 
 

 

 

 

 

 

 

metHods (Continued) 

Figure 1. Timeline of health questionnaire, medical, and environmental surveys. 



JanMarMayJulSepNov JanMarMayJulSepNov JanMarMayJulSepNov JanMarMayJulSepNov JanMarMayJulSepNov JanMarMayJulSepNov JanMarMayJulSepNov 

2001 2002 2003 2004 2005 2006 2007 

7/01: HHE 

request 

9/01: 

Questionnaire I 

4/02: Environmental 

survey I 

6/02: Medical 

survey I 

8/04: Questionnaire II, 

Environmental survey II, 

Medical survey II 

8/05: Questionnaire III, 

Environmental survey III, 

Medical survey III 

8/07: Questionnaire IV 

Environmental survey IV 

survey (Figure 1). 

We selected respiratory case and comparison groups based on 

the responses to the initial health questionnaire survey in 2001 

and invited them to participate in the June 2002 medical survey. 

We defined the respiratory case group as those participants who 

reported one or more of the following: three or more of five asthma 

symptoms (wheeze, chest tightness, attacks of shortness of breath, 

coughing, and awakened by an attack of breathing difficulty) 

occurring weekly in the last 4 weeks; two or more hypersensitivity 

pneumonitis symptoms (fever and chills, flu-like achiness or achy 

joints, and shortness of breath hurrying on the level or walking 

up a slight hill) occurring weekly in the last 4 weeks; current 

physician-diagnosed asthma occurring after building occupancy; or 

physician-diagnosed hypersensitivity pneumonitis or sarcoidosis. 

We defined the comparison group as having none of the symptoms 

listed above in the last year, nor any of the specified diagnoses. On 

the basis of these criteria, we identified 202 employees who met the 

case definition and 154 employees who met the comparison group 

definition. The extended health questionnaire was administered 

by a trained interviewer on a computer and included questions 

on health symptoms and medical diagnoses, an extensive module 

on medication use, quality of life questions from a standardized 

questionnaire (SF-12 Health Survey), home and work environment, 

work history, demographic questions, and smoking history 

(questionnaires available upon request). The 2002 medical 

testing included spirometry, methacholine challenge testing or 

bronchodilator testing, allergen skin prick testing, exhaled nitric 

oxide, and exhaled breath condensate, which are detailed below. 

Health Hazard Evaluation Report 2001-0445-3141 Page 11 
metHods (Continued) 

In 2004, the cases and comparison group employees originally 

invited to participate in the 2002 medical survey, and still currently 

employed in the building, were offered a repeat extended health 

questionnaire and medical testing (spirometry, methacholine 

challenge testing or bronchodilator testing, and allergen skin prick 

testing, which are detailed below). Fifteen employees who had not 

been part of the original invitees, but who had volunteered to take 

part in the 2002 survey, were also invited in 2004. 

In 2005, an extended health questionnaire and the same medical 

testing as in 2004 was offered to the cases and comparison group 

employees defined in the 2001 survey and still currently employed 

in the building, employees who had not been part of the original 

invitees, but who had volunteered to take part in the 2002 and 

2004 surveys, and participants in the 2004 health questionnaire 

survey who met the respiratory case or comparison group 

definitions. We also randomly selected 300 employees (about 

20 employees on each floor of the building) to participate in the 

extended health questionnaire, allergen skin prick testing, and 

two additional tests–nasal nitric oxide and nasal lavage, which are 

detailed below. Of these 300 employees, 139 were part of the group 

offered all medical tests. 

Written informed consent was obtained from each subject before 

each medical visit. All medical tests were approved by the NIOSH 

Human Subjects Review Board. 

Spirometry 

NIOSH technicians performed spirometry tests (breathing 

tests) using a dry rolling-seal spirometer interfaced to a personal 

computer and following American Thoracic Society guidelines 

(ATS 1995), with an abnormal test result being defined as being 

below the lower limit of normal (Hankinson et al. 1999). Each 

participant’s largest FVC and FEV1

 were selected for analysis. 

Obstruction was defined as an FEV1

/FVC ratio and FEV1 below 

the lower limits of normal with a normal FVC. Borderline 

obstruction was defined as an FEV1

/FVC ratio below the lower 

limits of normal with a normal FEV1

 and FVC. Restriction was 

defined as an FVC below the lower limit of normal with a normal 

FEV1

/FVC ratio. A mixed pattern (obstruction and restriction) was 

defined as an FEV1

/FVC ratio, FEV1, and FVC below the lower 

limits of normal. Employees with evidence of airways obstruction 

or a mixed pattern were administered albuterol; a bronchodilator 

medication used to treat obstructive lung diseases such as asthma, 

Page 12 Health Hazard Evaluation Report 2001-0445-3141 
metHods (Continued) 

and were then re-tested to see if the obstruction was reversible. 

Reversible obstruction was defined as an improvement in the 

FEV1

 of at least 12% and at least 200 mL after administration of 

albuterol. 

Methacholine Challenge Testing 

The methacholine challenge test measures the presence and 

degree of non-specific bronchial hyper-reactivity which is common 

among persons with asthma. To detect bronchial hyper-reactivity, 

methacholine challenge testing was performed using standardized 

techniques (Crapo et al. 2000) with five different doses (0.125, 

0.5, 2.0, 8.0, and 32.0 mg/mL) of methacholine. Five breaths of 

nebulized methacholine were administered for each dose, starting 

with 0.125 mg/mL, and spirometry was measured after the fifth 

breath. If the highest FEV1

 after any dose was greater than 80% of 

the highest baseline FEV1

, the next higher dose of methacholine 

was administered. If FEV1

 dropped more than 20% of the 

baseline value, no further methacholine was given. We calculated 

the provocative concentration of methacholine that causes an 

interpolated 20% decline in FEV1

 from baseline (PC20). Categories 

of bronchial hyper-reactivity were defined as follows (Crapo et al. 

2000): 

●	 PC20 less than or equal to 4.0 mg/mL – bronchial hyperreactivity 

●	 PC20 between 4.1 and 16.0 mg/mL – borderline bronchial 

hyper-reactivity 

●	 PC20 greater than 16 mg/mL – normal 

Skin Prick Testing 

Skin prick allergy testing was done with commercially available 

extracts of seven common indoor and outdoor allergens: dust 

mite mix, German cockroach, cat hair, grass mix, ragweed mix, 

common weed mix, and Eastern tree mix. In addition, we tested 

for sensitivity to three commercially available mold mixes: 

Dematiaceae, Aspergillus, and Penicillium. The Greer DermaPIK 

method was used for the skin allergy testing. The Greer DermaPIK 

is a plastic, single use device with six tiny tines arranged at the tip 

in a 2 millimeter circle for epicutaneous allergy skin testing. The 

allergens were placed on the forearm of the subject, along with a 

positive (histamine) and negative control (glycerin in water). After 

Health Hazard Evaluation Report 2001-0445-3141	 Page 13 
metHods (Continued) 

15 minutes, each response wheal length and width was measured 

to the nearest millimeter and recorded. For each wheal, the mean 

diameter (average of the length and width) was calculated. A 

positive reaction to an allergen was defined as an average diameter 

at least 3 millimeters larger than the negative control and greater 

than 25% of the average diameter of the positive control. For the 

purposes of this study, atopy was defined as at least one positive 

skin test on allergy testing (excluding the mold mixes). 

Exhaled Nitric Oxide 

Nitric oxide gas, produced by various cells within the respiratory 

tract, is detectable in the exhaled air. In persons with poorly 

controlled allergic asthma, exhaled nitric oxide concentrations 

are high. Nitric oxide was measured off-line using standardized 

techniques (ATS 1999), and the procedure has been documented 

elsewhere (Akpinar-Elci et al. 2008). For this report we compared 

mean levels between participants based on symptomatic status. We 

also used a cut-off point of 9 parts per billion or greater as higher 

than normal (Kharitonov et al. 1997). However, the upper limit of 

normal exhaled nitric oxide has not yet been established. 

Exhaled Breath Condensate 

Exhaled breath condensate testing was being evaluated as a 

noninvasive way of measuring inflammation in the airways. 

Exhaled breath condensate was collected over a 15 minute period 

from subjects using previously published techniques (Mutlu et 

al. 2001). We measured IL-8 and nitrite in the exhaled breath, 

which may represent biomarkers of pathological processes such 

as inflammation in the lungs (Kharitonov and Barnes 2001). 

Nitrite was measured per manufacturer’s recommendations 

using an ozone chemiluminescence nitric oxide analyzer (Model 

280, Sievers, Boulder, Colorado), and IL-8 was measured using 

a chemiluminescent immunoassay (QuantiGlo, R & D Systems, 

Minneapolis, Minnesota). 

Nasal Nitric Oxide 

In 2005, we tested for nasal nitric oxide to look for inflammation 

in the upper respiratory airways. Nasal nitric oxide was measured 

on-line using standardized techniques with a rapid-response 

chemiluminescence analyzer (Sievers Instruments model 280, 

Page 14 Health Hazard Evaluation Report 2001-0445-3141 
metHods (Continued) 

Boulder, Colorado) according to the 2005 American Thoracic 

Society guidelines (ATS 2005). Three measurements were recorded 

from each nostril. A two-point calibration was done each day using 

nitric oxide-free gas and 45 parts per million nitric oxide precision 

gas. We asked pre-test questions to exclude possible confounding 

factors for nitric oxide measurements such as smoking within the 

last hour, any nitrate containing food within the last two hours, or 

having a recent respiratory infection. We rescheduled those who 

had a positive response to any one of these confounders. Subjects 

completed five repeated humming maneuvers, immediately before 

measurement. A latex nasal olive connected to a filter and a 

respirator tube with a connector was gently introduced into the 

right naris. Each subject closed his/her velum by holding his/her 

breath throughout the measurement. Room air entered through 

the left nostril and was aspirated from the right nostril at 5 liters 

per minute constant transnasal flow. To achieve a plateau of nasal 

nitric oxide, 20 to 30 seconds of breath holding was sufficient 

(ATS 2005; Maniscalco, Sofia et al. 2003; Maniscalco, Weitzberg et 

al. 2003; Vural et al. 2002). 

Nasal Lavage 

We also conducted nasal lavage (washing) testing in 2005 to 

determine if markers of inflammation were associated with selfreported symptoms in subjects. We used collection methods for 

nasal lavage fluid as described by Hirvonen et al. (1999). Fluid 

recovered in the collection plate from the nares was combined and 

the volume was measured. Nasal lavage fluids were centrifuged 

for 10 minutes at a relative centrifugal force of 600 x gravity. The 

supernatant fluids were separated from the cell pellets, divided 

into aliquots, and frozen on dry ice for shipment back to the 

laboratory. In the laboratory, the supernatant fluids were stored at 

-80 degrees Celsius until analysis. Cell pellets were suspended in 

30 mL Cytolyte® (Cytyc Inc., Marlborough, Massachusetts), and 

stored at 4 degrees Celsius. Cell /Cytolyt® samples were vortexed 

for 10 minutes and then centrifuged for 10 minutes at 600 x 

gravity. Cell pellets were resuspended in 20 mL Preservcyt®(Cytyc 

Inc.) and cytology slides made using a Thin Prep Processor®(Cytyc 

Inc.) using the mucoid sample setting. The volume of sample 

transferred to the glass slide was recorded. Slides were stained 

(Diff Quick Stain Kit, IMEB Inc., San Marcos, California), and 

inflammatory cells were counted on > 20 visual fields. Counts for 

each cell type were adjusted for fraction of total sample used, area 

of the visual field, and total area of the cytology spot to provide a 

semi-quantitative assessment of nasal inflammatory cell content. 

Health Hazard Evaluation Report 2001-0445-3141 Page 15 
metHods (Continued) 

Albumin (Bethyl Labs, Montgomery, Texas), myleoperoxidase 

(Assay Designs, Ann Arbor, Michigan), IL-8 (R&D, Minneapolis, 

Minnesota – chemiluminescent ELISA), and eosinophilic cationic 

protein (Phadia AutoCap (CAP) System, formerly Pharmacia, 

Uppsala, Sweden) immunoassays were performed according to the 

manufacturer’s instructions on each nasal lavage supernatant fluid, 

in duplicate. 

Reporting of Individual Medical Testing Results 

After each medical survey, letters providing individual test results 

and interpretations of spirometry, methacholine or bronchodilator 

testing, and skin prick testing were mailed to each participant’s 

home address. For individuals with abnormal results, guidance and 

recommendations for additional medical follow-up were provided. 

Environmental Surveys 

We conducted environmental sampling at four different time 

points during the study period: April 2002, August 2004, August 

2005, and August 2007. Additionally, in December 2001, we 

collected carpet dust samples from the 17th floor, just prior to the 

carpet being replaced to compare levels of microbial agents in the 

new carpets to the old carpets. In April 2002, we collected both 

carpet and chair dust samples from workstations of 338 case and 

comparison group employees, including re-sampling the 17th floor. 

If a case or comparison group employee had moved during the 

past 12 months, we also collected a sample from the employee’s 

previous workstation. In August 2004, we collected dust samples 

from the workstations of the 2002 case and comparison groups 

if they were still employed in the building (n = 279). Before the 

2004 survey, we received current seating plans from the agencies 

and compared the employee names we had from the previous 

2002 survey for the selected locations. If a selected employee 

had changed workstations, we changed our sample to the new 

location. In August 2005, we randomly selected 300 workstations 

stratified by floor and collected floor dust samples if the selected 

workstations were occupied. In August 2007, we re-sampled 150 of 

the 300 locations sampled in 2005. Information on the number 

of workstations by floor is detailed in Table 1. The number of 

workstations with repeated samples by floor during the four 

environmental surveys is shown in Table 2. 

Page 16 Health Hazard Evaluation Report 2001-0445-3141 
metHods (Continued) 

Table 1. Number of sampled workstations by floor and survey* 

Floor 

Total no. of 

unique sampled 

workstations over 

four surveys† 

No. of sampled 

workstations in 

the 2002 

survey 

No. of sampled 

workstations in 

the 2004 

survey 

No. of sampled 

workstations in the 

2005 

survey 

No. of sampled 

workstations in 

the 2007 

survey 

Total 689 338 279 297‡ 150 

5 24 4 6 20 4 

6 60 30 23 21 10 

7 55 30 22 21 11 

8 39 21 16 19 11 

9 53 26 22 21 12 

10 51 28 25 21 10 

11 40 16 15 21 11 

12 44 19 14 21 10 

14 57 30 23 20 10 

15 54 27 25 20 10 

16 32 8 7 21 10 

17 79 58 46 21 14 

18 50 20 20 21 12 

19 44 20 14 22 12 

20 7 1 1 7 3 

* No workstation was sampled more than once in any given survey year. 

† Workstations sampled at least once during the four surveys. 

‡ We were not able to identify correct workstations for three employees. 

Table 2. Number of sampled workstations by number of replicate samples and floor* 

Floor 

Total no. of 

unique sampled 

workstations over 

four surveys†

 No. of sampled 

workstations with 

one sample 

No. of sampled 

workstations with 

two replicate 

samples 

No. of sampled 

workstations with 

three replicate 

samples 

No. of sampled 

workstations with 

four replicate 

samples 

Total 689 379 261 33 16 

5 24 15 8 1 0 

6 60 38 20 2 0 

7 55 30 22 2 1 

8 39 19 14 4 2 

9 53 32 17 1 3 

10 51 22 26 2 1 

11 40 20 18 1 1 

12 44 28 14 0 2 

14 57 35 18 4 0 

15 54 30 21 2 1 

16 32 20 10 2 0 

17 79 31 37 10 1 

18 50 30 18 1 1 

19 44 25 16 1 2 

20 7 4 2 0 1 

* No workstation was sampled more than once in any given survey year. 

† Number of dust samples taken from the same workstation across the four surveys. 

Health Hazard Evaluation Report 2001-0445-3141 Page 17 
metHods (Continued) 

In 2002 and 2004, both chair and floor dust samples from each 

workstation were collected. In 2005 and 2007 only floor dust 

samples were collected. 

In the 2002, 2004, and 2007 environmental surveys, floor or chair 

dust was collected onto polyethylene filter socks (Midwest Filtration 

Company, Fairfield, Ohio) with a crevice tool and a L’il HummerTM 

backpack vacuum (100 CFM, 1.5 horse power, Pro-Team Inc., 

Boise, Idaho). Each crevice tool for an individual sampling location 

was cleaned with isopropyl alcohol before sampling. For each 

sampling location, one chair (seat, back support, and armrest) was 

vacuumed for 3 minutes and a 2 m2

 carpeted floor area within the 

workstation (around where the chair was located) was vacuumed 

for 5 minutes using different crevice tools. The samples were sealed 

in plastic bags and transported to the laboratory where collected 

dusts in the filter socks were emptied into 50 mL pyrogen-free 

conical tubes. Hair, fluff, and other larger objects were removed 

from the samples, which was then homogenized by rotation on 

a 360-degree rotary arm shaker at 65 rotations per minute for 

2 hours. The dust samples were then weighed, partitioned, and 

sent for analyses of culturable fungi, endotoxin, ergosterol, cat 

allergen, and dog allergen. The samples for fungi were cultured 

with malt extract, dichloran glycerol 18, and cellulose agars at 

room temperature for 7–10 days. Total culturable fungi were 

reported as CFU per mg dust and also per m2

 (for floor samples) 

or per chair (for chair samples) by multiplying the resulting CFU 

per mg value by the total amount of dust collected in each floor 

(or chair) sample and then dividing by 2 m2

 for floor samples. 

Dog and cat allergens were analyzed with an enzyme-linked 

immunosorbent assay, and reported as μg per mg dust, and also 

as per m2

 or per chair. Endotoxin samples were analyzed with 

the Limulus amoebocyte lysate assay using kinetic QCL methods 

(Chun et al. 2002), and the results were reported as EU per mg 

dust, and also as per m2

 or per chair. Ergosterol was analyzed with 

gas chromatography-mass spectrometry and reported as ng per mg 

dust, and also as per m2

 or per chair. In 2005, we used the High 

Volume Small Surface Sampler to collect floor dust in the cyclone 

catch cup from 2 m2

 carpeted areas. The collected dust samples in 

2005 were processed in the same way as above and analyzed for all 

the microbial agents except for ergosterol. The 2005 and 2007 dust 

samples were also analyzed for (1→3)-β-D-glucan and culturable 

bacteria [Gram-positive and Gram-negative bacteria]. 

We reviewed 12 unpublished building assessment reports by 

environmental consultants and newsletters by the building 

Page 18 Health Hazard Evaluation Report 2001-0445-3141 
metHods (Continued) 

management since 2000 to obtain historical information on 

water damage and remediation. We defined remediation activity 

as elimination of sources of water infiltration, such as building 

exterior (window and balcony) repairs and roof coping or 

replacement, or replacement of water-damaged materials such as 

carpet and wallboard. Building exterior repairs around window 

openings included construction activities, such as brick caulking, 

window flashing, parapet coping, and plastic barrier repair. We 

did not include surface cleaning as a type of remediation because 

a thorough cleaning was done on all the floors of the building in 

2004. We considered an employee’s workstation as “remediated” 

if the workstation was within 15 feet of a remediated section of 

exterior or interior walls. We considered all workstations on the 

floor as “remediated” where an entire floor carpet was replaced. 

All the workstations on the 19th and 20th floors directly underneath 

the roof were considered “remediated” when the roof was replaced 

or repaired. We used a linear regression model that accounted 

for correlation of repeated measurements within the same 

sampled workstations across the surveys to examine remediation 

effectiveness on total and hydrophilic levels of culturable fungi, 

including the fraction of hydrophilic fungi, as well as endotoxin 

and cat and dog allergens (Cho et al. 2011). 

Statistical Analysis 

Since participants may have reported different dates of diagnoses, 

dates of birth, and building occupancy dates in different 

questionnaires, the dates used for our analyses were set taking into 

account all dates reported. The date reported most frequently in 

the questionnaires was the one used. If there was not one date 

reported most frequently, we used the date given in the earliest 

questionnaire completed. 

Definitions of Health Outcomes 

We defined epidemiological asthma (“epi-asthma”) as having either 

post-occupancy current asthma or having at least three or more 

lower respiratory symptoms (wheeze, chest tightness, coughing, 

attacks of shortness of breath, or being awakened by an attack 

of breathing difficulty) at least once a week in the last 4 weeks. 

We defined “asthma symptoms” as having two or more lower 

respiratory symptoms occurring one or more times per week in 

the last 4 weeks, and “BR asthma symptoms” as asthma symptoms 

with at least one symptom which improved when away from the 

Health Hazard Evaluation Report 2001-0445-3141 Page 19 
metHods (Continued) 

building. Hypersensitivity pneumonitis symptoms (“hypersensitivity 

pneumonitis-like symptoms”) were defined as having two or more 

of the following: fever and chills, flu-like achiness or achy joints, 

or shortness of breath while hurrying on the level or walking up a 

slight hill (“shortness of breath on exertion”) at least one or more 

times per week in the last 4 weeks. Nasal symptoms included stuffy, 

itchy, or runny nose, or sneezing, and sinus symptoms consisted of 

sinusitis or sinus problems. “Rhinosinusitis symptoms” consisted 

of one or more nasal or sinus symptoms occurring at least once 

every week in the last 4 weeks. We defined “BR rhinosinusitis 

symptoms” as rhinosinusitis symptoms with at least one symptom 

which improved when away from the building. 

Cross-Sectional Data Analysis 

For the health questionnaires in all four survey years, we 

compared lower respiratory, nasal, sinus, and eye symptoms, as 

well as physician-diagnosed asthma, to data from the U.S. adult 

population based on the third National Health and Nutrition 

Examination Survey (CDC 1996). We also compared asthma 

prevalences to the adult population in Connecticut, based on 

data from the Behavioral Risk Factor Surveillance System (CDC 

2007). Finally, we compared the prevalence of work-related 

symptoms occurring weekly in the last 4 weeks to U.S. office 

workers in buildings without known indoor air quality problems 

(Environmental Protection Agency Building Assessment Survey 

Evaluation study) (Erdmann and Apte 2004; Brightman et al. 

2008). We calculated 95% CIs using a method which assumes 

that the observed data are from a Poisson distribution (Kahn and 

Sempos 1989). The results and discussion of these analyses have 

been sent to requestors as interim letters and reports which are 

available upon request. 

Major remediation was reportedly completed by early 2004. Thus, 

we examined whether remediation had an impact on the health 

status of employees. We compared the prevalence of symptoms in 

two groups of employees using 2005 and 2007 health questionnaire 

survey participants–persons who were in the building prior to 

January 2004 (long-term), and those who came to the building in 

January 2004 or later (short-term). 

For environmental and epidemiologic analyses, we grouped 

culturable fungi into either “hydrophilic fungi” (Aw ≥ 0.9, Aw: the 

amount of free or available water in substrates), “mesophilic fungi” 

(0.8 ≤ Aw < 0.9), either “hydrophilic or mesophilic” (Aw ≥ 0.8), 

Page 20 Health Hazard Evaluation Report 2001-0445-3141 
metHods (Continued) 

or “other fungi” (not meeting either mesophilic or hydrophilic 

classifications) (Burge and Otten 1999; Flannigan and Miller 2001; 

Grant et al. 1989). 

We examined the association between exposure to microbial 

agents in the building and employees’ respiratory illnesses. For the 

cross-sectional epidemiologic analysis using all 888 initial 2001 

health questionnaire participants, we calculated floor averages 

for fungal and endotoxin measurements and ranked them into 

tertiles (low, medium, or high exposure floors). Then, we assigned 

participants from the 2001 questionnaire to one of the tertiles 

based on the floor they spent the majority of their time on, since 

not all participants had individual workstation measurements (Park 

et al. 2006). We used logistic regression models, adjusting for age, 

gender, race, smoking status, and tenure in the building. 

We performed an additional analysis using only 323 participants 

who met the respiratory case or comparison group definitions 

(as defined above) from the 2001 survey. In this analysis, we 

used individual workstation measurements for fungi, endotoxin, 

ergosterol, and cat and dog allergens as their personal exposures 

(Park et al. 2008). We used logistic regression models, adjusting for 

age, gender, race, smoking status, and tenure, using both single and 

multiple microbial measurements as exposures of interest in the 

model. 

To determine adult-onset asthma incidence rates in the years before 

and after major remediation was completed, we did an incidence 

rate analysis using the 2007 cross-sectional survey participants and 

calculated person-time at risk for three different time periods: from 

16 years of age to building occupancy, from building occupancy 

to January 1, 2004 (when major remediation was reportedly 

completed), and from January 1, 2004 to the 2007 survey date. For 

participants with physician-diagnosed adult-onset asthma, time at 

risk ended on the month and year of diagnosis. Participants with 

childhood asthma (diagnosed before age 16) did not contribute any 

time at risk. 

We also used logistic regression models to analyze results from 

the 2007 questionnaire and environmental surveys. As we did for 

the 2001/2002 cross-sectional study analysis, we assigned all 2007 

health questionnaire survey participants to low, medium, or high 

exposure tertiles, based on the floor where they spent the majority 

of their time. We adjusted the models for the same parameters, 

with the exception of race, which wasn’t significant in the final 

model. 

Health Hazard Evaluation Report 2001-0445-3141 Page 21 
metHods (Continued) 

Repeated Measurement Data Analysis 

To evaluate trends in symptom prevalence over time among those 

who participated in all four surveys, we used repeated measure 

models to identify significant differences between survey years. 

To evaluate trends of newly reported cases, we used all four health 

questionnaire surveys to identify reported post-occupancy onset 

asthma, hypersensitivity pneumonitis, and sarcoidosis in the 

building by year since the building was occupied in 1994. 

To examine changes of participants’ health over time, we analyzed 

persons who participated in both the 2002 and 2005 medical 

surveys (n = 97) (Iossifova et al. 2011). In this analysis, we redefined 

respiratory cases based on 2002 questionnaire responses, using 

the same criteria as those used for the 2001 health questionnaire 

survey. 

We examined the effect of remediation on both qualitative species 

and quantitative fungal information in the floor dust, including 

the proportion of fungi classified as hydrophilic or mesophilic. 

From our review of 12 unpublished building assessment reports 

by environmental consultants and newsletters by the building 

management since 2000, we obtained historical information on 

water damage and remediation. Remediation activities considered 

in this analysis included work related to eliminating sources of 

water and replacing damaged building materials. For the repeated 

measurement analysis, we used more complex regression models 

to account for a random effect of employees’ workstations with 

environmental samples (Cho et al. 2011). 

We also examined the prevalence of lower respiratory, 

rhinosinusitis, throat, eye, skin, and systemic symptoms among 

persons who participated in all four health questionnaire surveys 

(n = 258). In this analysis, we categorized the symptomatic 

participants into two groups based on time of symptom 

occurrence–the recent and frequent symptom group: those who 

reported respiratory symptoms occurring one or more times per 

week in the last 4 weeks; and the less recent symptom group: those 

who reported respiratory symptoms in the last 12 months but not 

in the last 4 weeks. 

In three subsequent cross-sectional surveys after the initial 

evaluation of the building, we examined whether occupants who 

reported BR rhinosinusitis symptoms in 2001 were more likely to 

Page 22 Health Hazard Evaluation Report 2001-0445-3141 
metHods (Continued) 

develop physician-diagnosed asthma or BR asthma symptoms than 

those with no BR rhinosinusitis symptoms. We also examined 

how microbial exposures interacted with the presence of BR 

rhinosinusitis symptoms in the development of asthma or BR 

asthma symptoms in the building occupants during the subsequent 

6 years of follow-up. 

We performed repeated measurement analysis using logistic 

regression models to examine the associations between 2002 

microbial exposure and respiratory health using all four health 

surveys. These models account for within-participant variability 

based on repeated measurements of health symptoms for each 

subject. 

To examine whether the odds of BR respiratory symptoms in the 

last 4 weeks changed over time, we used logistic regression models 

with repeated measurements of health where survey year was 

considered continuous (coded 1, 4, 5, and 7), after controlling 

for microbial exposures (fixed 2002 floor averages of total fungi, 

ergosterol, and endotoxin), age, gender, race/ethnicity, smoking 

status, and duration of building occupancy. Time trends for BR 

respiratory symptoms in the last 4 weeks were reported as ORs 

(95% CIs). 

To examine whether BR respiratory symptom severity at the 

individual level changed over time, we created a symptom severity 

score variable by coding “0” for no BR respiratory symptom, “1” 

for those who reported BR ‘less recent’ symptoms, and “2” for 

those who reported BR ‘recent and frequent’ symptoms for each 

survey. We used the same logistic regression models with repeated 

measurements where symptom score was considered a continuous 

dependent variable and survey year was considered a continuous 

independent variable, after controlling for microbial exposures, 

age, gender, race/ethnicity, smoking status, and duration of 

building occupancy. 

We reported all results as ORs with 95% CIs. There is an increased 

risk of association if the OR is greater than one, whereas an OR 

of one shows no association. A 95% CI means that there is a 95% 

chance that the true estimate is somewhere between the lower and 

upper limits. The OR is considered statistically significant if the CI 

does not contain one. 

All data analyses for this final report were done using SAS® 

System for Windows, version 9.2 (SAS Institute Inc., Cary, North 

Carolina). 

Health Hazard Evaluation Report 2001-0445-3141 Page 23 
 

 

 

Results 

Health Questionnaire Surveys (2001-2007) 

Participation and Demographics 

Participation in the health questionnaire surveys ranged from 

60% to 67% for the four surveys. The total number of employees 

participating in at least one survey was 1,494, of whom 900 

(60%) participated in more than one. Seventeen percent 

(n=258) participated in all four surveys. Demographics of survey 

participants were similar for the 4 years studied, with the exception 

of tenure which increased over the four surveys, as would be 

expected (Table 3). 

Table 3. Participation and characteristics of participants in the four health questionnaires 

(2001–2007) 

Outcome 2001 

(n = 888) 

2004 

(n = 771) 

2005 

(n = 797) 

2007 

(n = 762) 

Participation 67% 67% 66% 60% 

Age (mean ± SD) 45.9 ± 8.7 47.8 ± 8.0 48.6 ± 7.8 48.6 ± 8.4 

Gender 

Female 59% 

(519/887) 

58% 

(446/770) 

55% 

(442/797) 

57% 

(438/762) 

Building tenure (mean ± SD)* 5.9 ± 1.9 8.0 ± 3.0 8.7 ± 3.3 9.4 ± 4.6 

Race

 White 

Black 

Other 

77% 

(651/844) 

18% 

(156/844) 

4% 

(37/844) 

78% 

(592/760) 

18% 

(136/760) 

4% 

(32/760) 

81% 

(625/776) 

15% 

(118/776) 

4% 

(33/776) 

80% 

(594/747) 

17% 

(126/747) 

4% 

(27/747) 

Ethnicity 

Hispanic 6% 

(52/857) 

6% 

(47/763) 

7% 

(55/790) 

7% 

(57/762) 

Smoking status 

Current 

Former 

Never 

14% 

(124/888) 

26% 

(235/888)

60% 

(529/888)

11% 

(87/766) 

27% 

 (205/766)

62% 

 (474/766) 

11% 

(85/769) 

28% 

 (214/769)

61% 

(470/769)

9% 

(69/738) 

28%

 (205/738) 

63%

 (464/738) 

* Assumed continuous building tenure; 64 participants left the building and returned sometime between 

2001 and 2007. 

Page 24 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

Initial Cross-Sectional Health Questionnaire Survey 

in 2001 

From the initial cross-sectional survey in September 2001, we 

found an excess of respiratory symptoms and physician-diagnosed 

asthma reported among participants. In comparison with the U.S. 

adult population, wheezing, lifetime asthma, and current asthma 

were 2.2 to 2.5 times higher than expected (p < 0.05). Nasal and 

eye symptoms were also significantly elevated in the building, but 

to a lesser extent (1.5–1.6 times higher). The rate of post-occupancy 

asthma was 7.5 times higher than the rate of pre-occupancy adultonset asthma, indicating a large increase in asthma incidence in 

the period after building occupancy (Cox-Ganser et al. 2005). 

Subsequent Cross-Sectional Health Questionnaire 

Surveys in 2004, 2005, and 2007 

NIOSH conducted three subsequent cross-sectional surveys 

offered to all employees in 2004, 2005, and 2007. Rates of lower 

respiratory symptoms and asthma remained elevated when 

compared to national rates. 

Long-term employees (who occupied the building prior to January 

2004) comprise the majority of the participants; approximately 

88% or 1272/1447 had been in the building prior to January 2004. 

Only about 12% (175/1447) had come to the building in January 

2004 or later. Figure 2 shows lower respiratory, rhinosinusitis, and 

hypersensitivity pneumonitis-like symptoms for these two groups of 

employees. The long-term employee group had a higher prevalence 

of symptoms in both the 2005 and 2007 surveys, although only 

rhinosinusitis symptoms in 2005 and hypersensitivity pneumonitislike symptoms in 2007 were significantly higher. We did not 

perform the same analysis with the 2004 survey results because we 

had only a small number (n = 12) of short-term employees for the 

comparison. 

Health Hazard Evaluation Report 2001-0445-3141 Page 25 
 

 

Results (Continued) 

0 

10 

20 

30 

40 

50 

60 

70 

80 

Hypersensitivity 

pneumonitis-like 

symptoms 

Asthma 

symptoms 

Rhinosinusitis 

symptoms 

Hypersensitivity 

pneumonitis-like 

symptoms 

Asthma 

symptoms 

Rhinosinusitis 

symptoms 

2005 2007 

Prevalence (%) 

Pre 1/04 

Post 1/04 

*

*

* p<0.05, based on chi-square 

Figure 2. Comparison of respiratory symptoms prevalence by occupancy status 

(2005 and 2007). 


 

Incidence Rate Analysis Using the 2007 Health 

Questionnaire Survey Participants 

Using the 2007 health questionnaire survey results, we compared 

the incidence rate of post-occupancy adult-onset asthma, both 

before and after major remediation was completed, with the 

incidence rate of pre-occupancy adult-onset asthma. We found the 

rate between building occupancy and January 2004, when major 

remediation was reportedly completed, to be the highest, with a 

rate of 16.0 cases per 1,000 person-years. This was approximately 

5.5 times higher than the pre-occupancy rate which was 2.9 

cases per 1,000 person-years. The asthma incidence rate for the 

period between January 2004 and the end of the study period was 

12.0 cases per 1,000 person years, which was lower than before 

remediation, but still 4.1 times higher than the pre-occupancy 

adult-onset asthma rate. Both post-occupancy adult-onset rates were 

significantly higher than the pre-occupancy adult-onset rate (p < 

0.001). 

Page 26 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

Repeated Measurement Analysis of All Four 

Surveys 

Figures 3, 4, and 5 show the prevalence of respiratory and other 

symptoms among employees who participated in all four health 

questionnaire surveys (n = 258) by the less recent, and recent and 

frequent symptoms groups. The decrease in less recent symptoms 

from 2001 to 2004 was significant at p < 0.05 for wheeze, cough, 

and shortness of breath on exertion, and marginally significant 

at p < 0.10 for chest tightness, attacks of shortness of breath, and 

awakened with breathing difficulty. The increase in less recent 

symptoms from 2004 to 2005 was significant at p < 0.05 for 

chest tightness, cough, and shortness of breath on exertion, and 

marginally significant at p < 0.10 for fever and chills. The decrease 

in less recent symptoms from 2005 to 2007 was significant at p < 

0.05 for chest tightness and marginally significant at the p < 0.10 

level for sinus symptoms. 

Recent and frequent symptoms did not tend to show decreases 

in 2004 as compared to 2001. However, there were indications 

of increases in these symptoms from 2001 to 2005. This was 

significant at the p < 0.05 level for wheeze, attacks of shortness 

of breath, shortness of breath on exertion, nose and sneezing 

symptoms, and rash or itchy skin. The trend toward decreases in 

2007 as compared to 2005 was significant at p < 0.05 for awakened 

with breathing difficulty and rash or itchy skin, and marginally 

significant at p < 0.10 for attacks of shortness of breath and nose 

and sneezing symptoms. 

Health Hazard Evaluation Report 2001-0445-3141 Page 27 
Results (Continued) 

Figure 3. Prevalences of lower respiratory symptoms among those who participated in all four surveys by recent and frequent and less recent symptoms groups. 

50

40 35 30 25 20 15 10 

2001 2004 2005 2007 2001 2004 2005 2007 2001 2004 2005 2007 

50

40 35 30 25 20 15 10 

2001 2004 2005 2007 2001 2004 2005 2007 2001 2004 2005 2007 

Less recent symptomsRecent & frequent symptoms 

Wheeze Chest tightness Cough 

Attacks of shortness of breath Awakened with breathing difficulty Shortness of breath on exertion 

Percent 

Page 28 Health Hazard Evaluation Report 2001-0445-3141 
Results 

(Continued) 

Figure 4. Prevalences of rhinosinusitis, throat, eye, and skin symptoms among those who participated in all four surveys by recent and frequent and less recent symptoms groups. 

0

80 70 60 50 40 30 20 10 

2001 2004 2005 2007 2001 2004 2005 2007 2001 2004 2005 2007 

0

80 70 60 50 40 30 20 10 

2001 2004 2005 2007 2001 2004 2005 2007 

Less recent symptomsRecent & frequent symptoms 

Nose and sneezing Sinus symptoms Throat symptoms 

Eye symptoms Rash or itchy skin 

t n ce reP

Health Hazard Evaluation Report 2001-0445-3141 Page 29
 
Results 

(Continued) 

0

60 50 40 30 20 10 

2001 2004 2005 2007 2001 2004 2005 2007 

Less recent symptomsRecent & frequent symptoms 

Percent 

Fever and chills Flu-like achiness 

Figure 5. Prevalences of systemic symptoms among those who participated in all four surveys by recent and frequent and less recent symptoms groups. 

Page 30 Health Hazard Evaluation Report 2001-0445-3141 
 

 

Results (Continued) 

Figures 6, 7, and 8 show the frequency of physician-diagnosed postoccupancy asthma, hypersensitivity pneumonitis, and sarcoidosis 

by diagnosis year. Through August 2007, a total of 145 postoccupancy asthma cases had been reported (Figure 6). The number 

of new asthma diagnoses peaked in 2000 and decreased since then. 

There have been a total of 27 hypersensitivity pneumonitis cases 

and 10 sarcoidosis cases reported through August 2007 since 

the building was occupied in 1994 (Figures 7 and 8). Incident 

hypersensitivity pneumonitis and sarcoidosis cases were highest in 

2001 and have decreased since then. By August 2007, there were 

only two post-occupancy asthma cases and two hypersensitivity 

pneumonitis cases that had been reported for that year. No new 

sarcoidosis cases had been reported during 2006 and the first 8 

months of 2007. 

Figure 6. Frequency of post-occupancy asthma diagnoses by year.* 

0 

10 

20 

30 

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 

Number of asthma cases 

*based on all participants from all surveys (n=1,494) Year 

*based on all participants from all surveys (n=1,494) 


 

Health Hazard Evaluation Report 2001-0445-3141 Page 31 
 

 

 

 

Results (Continued) 

Figure 7. Frequency of hypersensitivity pneumonitis diagnoses by year.* 

0 

1 

2 

3 

4 

5 

6 

7 

8 

9 

10 

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 

Number of HP cases 

*based on all participants from all surveys (n=1,494) Year 

*based on all participants from all surveys (n=1,494) 

Figure 8. Frequency of sarcoidosis diagnoses by year.* 

0 

1 

2 

3 

4 

5 

6 

7 

8 

9 

10 

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 

Number of sarcoidosis cases 

*based on all participants from all surveys (n=1,494) Year 

*based on all participants from all surveys (n=1,494) 

Among the 1,494 employees who participated in one or more 

surveys, 322 (22%) reported at least once ever being diagnosed 

with asthma. In comparison with prevalences reported from the 

2007 Behavioral Risk Factor Surveillance System in the state of 

Connecticut, after adjusting for gender, the risk of ever being 


 


 

Page 32 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

diagnosed with asthma was 1.5 times greater among occupants in 

the building (95% CI 1.3–1.7). 

The percentage of participants who reported current asthma by 

survey year ranged between 12% and 16% (Figure 9). Percentages 

are based on the number of participants that answered the 

question on physician-diagnosed asthma that was still present at 

the time of that particular survey. 

0 

5 

10 

15 

20 

25 

30 

2001 2004 2005 2007 

Prevalence (%) 

Year 

Figure 9. Prevalence of current asthma by survey year. 

From the analysis examining progression of rhinosinusitis 

symptoms in the initial survey to lower respiratory illnesses in the 

three subsequent surveys, we found that participants who reported 

BR rhinosinusitis symptoms in the initial 2001 survey were about 

twice as likely to have developed BR asthma symptoms (Table 4) in 

later surveys. The 2001 BR rhinosinusitis symptom group was also 

two times more likely to report new physician-diagnosed current 

asthma in later surveys but we did not obtain statistical significance 

due to the small number of new asthma cases (n=20). Polytomous 

logistic regression analysis showed that 2001 BR rhinosinusitis 

symptoms increased the risk for developing BR asthma symptoms 

by about twice, but not for developing non-BR asthma symptoms 

in any of the follow-up surveys. On the other hand, the group with 

non-BR rhinosinusitis symptoms tended to have an increased risk 

for developing non-BR asthma symptoms, but not for developing 

BR asthma symptoms. 

Health Hazard Evaluation Report 2001-0445-3141 Page 33 
Results (Continued)
 Table 4. Crude and adjusted odds ratios for developing BR asthma 

symptoms by follow-up survey in the 2001 BR rhinosinusitis symptom 

group* compared to the 2001 comparison group*
 

Year of 

follow-up survey 

Crude OR 

(95% CI) 

Adjusted OR 

(95% CI) 

Demographics† 

Adjusted OR 

(95% CI) 

Demographics and 

Environmental Exposure‡ 

2004 2.11 

(1.11, 4.00)§ 

2.00 

(1.02, 3.92)§ 

2.10 

(1.03, 4.31)§ 

2005 2.30 

(1.30, 4.08)§ 

2.26 

(1.23, 4.15)§ 

2.28 

(1.19, 4.36)§ 

2007 1.74 

(0.87, 3.51) 

1.76 

(0.86, 3.63) 

1.54 

(0.73, 3.25) 

Any follow-up 

survey 

2.00 

(1.27, 3.14)§ 

2.25 

(1.39, 3.66)§ 

2.24 

(1.34, 3.72)§ 

* The 2001 BR rhinosinusitis symptom group includes those who reported BR 

rhinosinusitis symptoms but no BR asthma symptoms in the initial 2001 survey, 

and the 2001 comparison group includes those who had neither BR rhinosinusitis 

nor BR asthma symptoms in the initial 2001 survey. 

† Race, gender, age, smoking status, and year of building occupancy 

‡ Tertile exposure (low/medium/high) is based on the rank order of floor-specific 

geometric means (per m2

 area) of culturable fungi, ergosterol, and endotoxin 

measured in the 2002 environmental survey. 

§ p < 0.05 

Medical Surveys (2002–2005) 

Participation and Demographics 

There were 522 persons who participated in at least one medical 

survey between 2002 and 2005. Approximately one-third (35% or 

185/522) participated in more than one survey. Only 76 (15%) 

participated in all three surveys. 

In 2002, there were 248 participants (233 from the 2001 

respiratory case and comparison groups, along with 15 volunteers) 

among those who were eligible for the medical survey. Participation 

was higher in the respiratory case group than the comparison 

group (70% vs. 59%, respectively). 

In 2004, 196 employees completed the medical testing. Among 

these participants, 144 persons had been originally selected as 

part of the respiratory case or comparison groups in 2001, seven 

had volunteered to participate in the 2002 medical survey, and 45 

employees volunteered in 2004. 

During the 2005 survey, 339 employees participated in at least one 

Page 34 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

part of the medical survey. Of these, 229 were part of either the 

original 2001 or 2004 respiratory case or comparison groups, 56 

were volunteers in 2005 or from earlier medical surveys, and 54 

were from the randomly selected group. 

Participation in the medical surveys ranged from 46% in 2005 

to 68% in 2002 (Table 5). In general, the characteristics of 

the participants were similar across the three surveys, with the 

exception of age and building tenure, both of which increased, as 

would be expected. 

Table 5. Characteristics of participants in the three medical survey 

questionnaires (2002–2005) 

Outcome 2002 

(n = 248) 

2004 

(n = 196) 

2005 

(n = 339) 

Participation 68% 60% 46% 

Age (Mean ± SD) 46.9 ± 8.4 47.7 ± 7.7 49.2 ± 7.5 

Gender

 Female 61% 

(152/248) 

65% 

(127/196) 

59% 

(199/339) 

Building tenure (Mean ± SD) 6.7 ± 1.7 8.6 ± 2.1 9.3 ± 2.8 

Race 

White 

Black 

Other 

74% 

(183/248) 

19% 

(47/248) 

7% 

(18/248) 

78% 

(153/196) 

18% 

(35/196) 

4% 

(8/196) 

79% 

(269/339) 

17% 

(58/339) 

4% 

(12/339) 

Ethnicity 

Hispanic 7% 

(17/248) 

5% 

(10/196) 

4% 

(13/339) 

Smoking status 

Current 

Former 

Never 

13% 

(32/248) 

28% 

(70/248) 

59% 

(146/248) 

13% 

(25/196) 

27% 

(52/196) 

61% 

(119/196) 

9% 

(30/339) 

31% 

(105/339) 

60% 

(204/339) 

Initial Medical Survey in June 2002 

On the basis of the results from the September 2001 survey, we 

decided to return to the building to conduct a more extensive 

questionnaire and medical testing in 2002. As noted in the 

methods, 356 employees were selected and invited to participate 

based on the presence or absence of various symptoms, and 

physician-diagnosed asthma, hypersensitivity pneumonitis or 

Health Hazard Evaluation Report 2001-0445-3141 Page 35 
 

Results (Continued) 

sarcoidosis. Among the participants, the respiratory cases had a 

higher prevalence of abnormal breathing tests and medication use 

(Cox-Ganser et al. 2005). 

Allergen skin prick testing was done to determine the percentage 

of participants that were atopic or had allergies to any one of the 

three mold mixes. Cox-Ganser et al. (2005) reported that over 

half of the participants in the 2002 medical survey were atopic. 

There was no difference in the prevalence of atopy between the 

respiratory case group and the comparison group. However, 

persons who reported pre-occupancy asthma were significantly 

more likely to be atopic than persons with no reported history of 

asthma or that had developed asthma after being in the building (p 

< 0.05). Persons with post-occupancy asthma were significantly less 

likely to have a reaction to any of the mold mixes (Cox-Ganser et 

al. 2005). 

Exhaled nitric oxide concentrations were not significantly different 

between the respiratory case and comparison groups, although 

participants with physician-diagnosed current asthma who had 

never smoked had significantly higher levels of exhaled nitric 

oxide (Interim Letter IV, available upon request). However, among 

non-smokers, levels of IL-8 were positively associated with several 

symptoms (cough, any lower respiratory symptom, BR lower 

respiratory symptom, sneezing, runny nose, any nasal symptom, 

and any sinus symptom) and physician diagnosed asthma (AkpinarElci et al. 2008). 

Subsequent Medical Surveys in August 2004 and 

August 2005 

Details on lung function testing and medication usage for the 

2004 and 2005 medical surveys can be found in the Interim letter 

VII (available upon request). The prevalence of abnormal lung 

function tests and medication use was higher among participants 

in the respiratory case group when compared to the comparison 

group as we found from the initial medical survey, showing that 

self-reported symptoms correlated well with objective lung tests and 

medication use. 

In the two subsequent surveys, we did not find any significant 

change in atopic status among participants who had an allergic 

skin test during the 2002 survey and another test in either 2004 or 

2005 (Interim letter VII, available upon request). 

Page 36 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

In 2005, nasal nitric oxide or nasal lavage collection was completed 

by 153 invited employees (51%). Of these 153 participants, 147 had 

interpretable nasal nitric oxide results. Of the 146 employees that 

participated in nasal lavage testing, 142 had results reported for 

eosinophilic cationic protein, IL-8, myeloperoxidase, or albumin. 

We found some association between upper airway symptoms 

and nasal inflammatory markers after adjusting for age, gender, 

race, smoking status, atopic status, and the use of any allergy 

medication in the last four weeks. Nasal congestion was marginally 

associated (p < 0.10) with IL-8 and significantly associated with 

myeloperoxidase (p < 0.05). Blowing out thick mucus was also 

associated with higher levels of IL-8 and eosinophilic cationic 

protein. We also found that participants who reported systemic 

symptoms, such as chills, flu-like achiness, or fatigue, had higher 

levels of nasal inflammatory markers, including IL-8, eosinophilic 

cationic protein, myeloperoxidase, and neutrophils. There was no 

statistically significant association between nasal nitric oxide levels 

and symptoms. 

Repeated Measurement Analysis of Medical 

Surveys 

From the analyses of those who participated in both the 2002 and 

2005 medical surveys, we observed no overall improvement over 

the interval in respiratory health, as reflected in symptom scores, 

overall medication use, spirometry abnormalities, or sick leave for 

either the 2002 respiratory case group (n = 54) or the 2002 noncase group (n = 43) (Table 6). Four employees went from borderline 

bronchial hyper-responsiveness to bronchial hyper-responsiveness; 

six developed abnormal spirometry; three reported incident postoccupancy current asthma, and four were newly diagnosed with 

hypersensitivity pneumonitis. Among the 2002 non-case group, the 

number of participants with lower respiratory symptoms increased 

from 16 in 2002 to 23 in 2005. However, the 2002 respiratory 

cases relocated in the building had a decrease in medication use 

and sick leave in 2005 compared with the non-relocated cases 

(Iossifova et al. 2011). Poorer quality of life was reported more 

frequently among the 2002 respiratory case group. There appeared 

to be some marginal improvement in emotional health among the 

2002 respiratory case group in 2005, whereas the 2002 non-cases 

reported more limitations in physical activities in 2005 compared 

to 2002 (Table 7). 

Health Hazard Evaluation Report 2001-0445-3141 Page 37 
Results (Continued) 

Table 6. Health characteristics among participants in both the 2002 and 2005 surveys, using 

only paired data from 2002 respiratory cases* and 2002 non-cases followed up in 2005 

Medical test 

Respiratory 

cases in 

2002 

(n = 54) 

Respiratory 

cases in 

2005 

(n = 54) 

Non-cases 

in 2002 

(n = 43) 

Non-cases in 

2005 

(n = 43) 

Bronchial hyper-responsiveness or positive 

bronchodilator test, % (n) 0 7% (2) 0 6% (2) 

FVC % predicted 96.1% 95.5% 100.8% 101.9% 

FEV1

 % predicted 93.6% 92.7% 99.9% 99.7% 

FEV1/FVC ratio 78.1% 77.2% 79.0%† 77.4%† 

Abnormal spirometry, % (n) 18% (8) 20% (9) 0† 11% (4)† 

LRS‡ point scale, mean (SD) 5.7 (3.6) 5.7 (3.8) 0.9 (1.4) 1.5 (2.4) 

Work-related LRS‡, % (n) 52% (28) 50% (27) 7% (3) 17% (7) 

Medication use scale, mean (SD) 1.7 (2.8) 1.1 (2.1) 0.2 (0.7) 0.3 (1.2) 

Oral steroid use in last 12 months, % (n) 22% (12)† 7% (4)† 5% (2) 0 

Inhaled steroid use in last 4 weeks, % (n) 15% (8) 13% (7) 2% (1) 2% (1) 

Beta-agonist use in last 4 weeks, % (n) 22% (12) 22% (12) 0 7% (3) 

Post-occupancy current asthma, % (n) 33% (18) 37% (20) 0 2% (1) 

Respiratory sick leave days, mean (SD) 4.6 (6.4)§ 6.3 (15.6)¶ 2.9 (9.6)** 2.0 (5.7)†† 

* Respiratory cases were redefined based on 2002 questionnaire responses, using the same criteria as those 

used for the 2001 health questionnaire survey.
 

† Change in health characteristic from 2002 to 2005 within a group was significant (p < 0.05).
 

‡ LRS: Lower respiratory symptoms (wheeze or whistling in the chest, chest tightness, shortness of breath, 

and cough occurring in the last 4 weeks).
 

§ Results after excluding an outlier who missed 110 days due to respiratory symptoms in 2005 are given as 

4.2 (5.6).
 

¶ Results after excluding an outlier who missed 110 days due to respiratory symptoms in 2005 are given as 

4.3 (6.2). 

** Results after excluding an outlier who missed 60 days due to respiratory symptoms in 2002 are given as 1.5 

(3.2).
 

†† Results after excluding an outlier who missed 60 days due to respiratory symptoms in 2002 are given as 

1.6 (5.0).
 

Page 38 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

Table 7. Quality of life among participants in both the 2002 and 2005 surveys, using 

only paired data from 2002 respiratory cases* and 2005 non-cases followed up in 2005 

Health characteristic 

Respiratory 

cases in 

2002 

(n = 54) 

Respiratory 

cases in 

2005 

(n = 54) 

Non-cases 

in 2002 

(n = 43) 

Non-cases 

in 2005 

(n = 43) 

General health fair to poor, % (n) 17% (9) 15% (8) 7% (3) 0 

Emotional health has limited kinds of 

activities, % (n) 41% (22)† 28% (15)† 9% (4) 2% (1) 

Emotional health has limited 

accomplishments, % (n) 50% (27)† 37% (20)† 17% (7) 14% (6) 

Physical health has limited kinds of 

activities, % (n)§ 48% (26) 41% (22) 0‡ 12% (5)‡ 

Physical health has limited 

accomplishments, % (n)§ 54% (29) 43% (23) 7% (3) 14% (6) 

Limited in climbing stairs, % (n) 48% (26) 57% (31) 9% (4) 19% (8) 

Limited in moderate activities, % (n) 30% (16) 31% (17) 5% (2) 5% (2) 

* Respiratory cases were redefined based on 2002 questionnaire responses, using the same criteria as 

those used for the 2001 health questionnaire survey. 

† p < 0.10, change from 2002 to 2005 within a group was marginally significant. 

‡ p < 0.05, change from 2002 to 2005 within a group was significant. 

§ p < 0.05, change from 2002 to 2005 between groups was significant. 

Environmental Results 

Comparison of Floor Dust Fungi Before and After 

the 17th Floor Carpet Replacement 

In December 2001, we collected floor dust samples from 61 

locations on the 17th floor before the carpet was replaced. In April 

2002, we returned to resample the 17th floor. We did not find a 

substantial reduction in fungi levels or in the types of fungal taxa 

(Interim letter III, available upon request). 

Initial Environmental Survey in 2002 

In April 2002 we returned to the building to sample workstations 

for respiratory cases and comparison group employees we had 

identified from the September 2001 survey. We were able to collect 

338 floor dust samples and 327 chair dust samples from 323 

employees’ workstations. We were not able to locate workstations 

of the other 29 participants. We identified 67 fungal species 

in the floor dust and 69 fungal species in the chair dust, along 

with unidentified species of Penicillium, yeasts (Rhodotorula and 

Sporobolomyces), and non-sporulating fungi. The GM of culturable 

fungi in floor dust was significantly lower than in chair dust (7,700 

Health Hazard Evaluation Report 2001-0445-3141 Page 39 
 

Results (Continued) 

CFU/g vs. 11,000 CFU/g, respectively). However, the levels of 

endotoxin and ergosterol were significantly higher in floor dust 

than chair dust. More detailed information on the findings of the 

environmental survey in April 2002 can be found in the article by 

Park et al. (2008). 

Follow-up Environmental Surveys in 2004, 2005, 

and 2007 

In general, the GMs of the microbial agents in the floor dust 

showed increasing trends across the 4 surveys with the lowest 

levels in 2002 (Table 8). The levels of cat and dog allergens (μg/ 

m2

) significantly decreased in the 2004 and 2007 surveys compared 

to the 2002 survey mostly due to an increasing percentage of 

samples below the LOD. The GMs of total culturable fungi (CFU/ 

m2

) in floor dust were 8 to 16 times higher in the 2007 survey 

as compared to those in the 2002, 2004, and 2005 surveys due 

to the increased levels of hydrophilic and mesophilic fungi, such 

as Phoma herbarum, yeasts, Aureobasidium pullulans, Cladosporium 

species, Alternaria alternata, and Epicoccum nigrum. For ergosterol, 

the primary sterol in the cell membrane of filamentous fungi and 

yeasts, the GM in 2007 was more than twice that in 2002. 

GMs of endotoxin in the 2005 and 2007 surveys (12,800 and 

12,000 EU/m2

, respectively) were about 5 times higher than that 

of the 2002 survey (2,700 EU/m2

). For Gram-negative bacteria, the 

difference in GMs (CFU/m2

) in floor dust between 2005 and 2007 

was more than one order of magnitude, which was mainly driven 

by increased levels on floors 14–17 in 2007 (data not shown). 

The upper floors where water leaks mainly occurred had 

significantly (p < 0.05) higher levels of hydrophilic fungi than 

the lower floors, except for the 2004 survey (Figure 10). Levels of 

Gram-negative bacteria on the upper floors were higher than those 

on the lower floors in 2007. 

Page 40 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

Table 8. Overall building average levels of microbial agents and cat and dog allergens in floor dust 

samples across 4 surveys 

Environmental parameter 2002 2002 2004 2004 2005 2005 2007 2007 

GM GM GM GM 

N (GSD) N (GSD) N (GSD) N (GSD) 

Total culturable fungi (CFU/m2

) 328 2,000 

(5.5) 

279 4,100 

(4.0) 

296 2,400 

(5.5) 

150 31,900 

(4.0) 

Ergosterol (ng/m2) 334 126.2 246 177.7 – – 143 304.9 

(3.9) (3.0) (2.1) 

Culturable Gram-negative – – – – 291 1,800 148 28,000 

bacteria (CFU/m2

) (10.5) (65.4) 

Endotoxin (EU/m2

) 338 2,700 276 6,100 294 12,800 142 12,000 

(4.8) (5.4) (5.6) (2.7) 

Cat allergen (Fel d 1) (μg/m2) 314 0.7 277 0.4 282 0.7 148 0.3 

(2.9) (3.4) (4.1) (6.2) 

Dog allergen (Can f 1)(μg/m2) 314 0.6 277 0.3 282 0.5 148 0.4 

(3.2) (3.6) (4.2) (3.9) 

Health Hazard Evaluation Report 2001-0445-3141 Page 41 
 

 

 

 

Results (Continued) 

Hydrophilic fungi (CFU/m2 ) 100 

101 

102 

103 

104 

105 

106 

107 

Lower floor (5-12) 

Upper floor (14-20) 

2002 2004 2005 2007 


 
 


Survey year 

Survey year 

Total gram-negative bacteria (CFU/m2 ) 100 

101 

102 

103 

104 

105 

106 

107 

108 

109 

1010 

Lower floor (5-12) 

Upper floor (14-20) 

2005 2007 




*p < 0.05, differences in log means between the lower (5–12) and upper (14–20) floors 

Figure 10. Observed levels of fungi and bacteria on the lower vs. 

upper floors by survey. No data available on Gram-negative bacteria 

in the 2002 and 2004 surveys. Each box plot: an IQR with median, 

upper and lower whiskers: upper and lower boundaries (3rd quartile 

/1st quartile ± 1.5 IQR). 

More details on environmental results for 2004, 2005, and 2007 

can be found in Interim letters VII and X, available upon request. 

Repeated Measurement Analysis of Environmental 

Surveys–Effect of Remediation 

We examined the effects of remediation on levels of culturable 

fungi in floor dust collected during the four cross-sectional 

environmental surveys. From these repeated measurement analyses, 

Page 42 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

we found significantly lower levels of total and hydrophilic fungi 

at remediated workstations than at non-remediated workstations 

in both 2004 and 2005 after completion of major remediation in 

early 2004 (Table 9). The remediation effect, however, disappeared 

by 2007. This finding was also supported by results from the 

qualitative analysis of fungal species that the fraction of hydrophilic 

to total fungal concentrations was lowest in 2004, increased again 

in 2005 and was highest in 2007 (Figure 11). The average fungal 

level in 2007 was ten-fold higher than those in previous surveys 

(Cho et al. 2011). 

Table 9. Adjusted mean levels of microbial agents* and mean fractions of 

hydrophilic fungi in floor dust by remediation and survey year 

Microbial agent Remediation 

2002 

Adjusted 

mean 

2004 

Adjusted 

mean 

2005 

Adjusted 

mean 

2007 

Adjusted 

mean 

Total fungi (CFU/m2

) Yes 1,251 2,773 1,000 36,326 

Total fungi (CFU/m2) No 2,265† 4,405† 2,561† 29,733 

Hydrophilic fungi 

(CFU/m2

) Yes 331 461 218 16,624 

Hydrophilic fungi 

(CFU/m2) No 837† 1,118† 783† 13,244 

Ergosterol (ng/m2

) Yes 160 178 – 250 

Ergosterol (ng/m2) No 109† 158 – 314 

Endotoxin (EU/m2

) Yes 6,007 3,671 11,051 11,242 

Endotoxin (EU/m2) No 1,938† 6,035† 11,500 10,861 

Cat allergen (μg/m2

) Yes 0.50 0.27 0.33 0.24 

Cat allergen (μg/m2) No 0.72‡ 0.42† 0.71† 0.26 

Dog allergen (μg/m2

) Yes 0.40 0.21 0.28 0.48 

Dog allergen (μg/m2) No 0.57‡ 0.25 0.54‡ 0.37 

Hydrophilic fungi 

fraction§ Yes 0.37 0.24 0.27 0.58 

Hydrophilic fungi 

fraction§ No 0.49 0.35 0.41 0.58 

* GMs of microbial agents estimated using regression models for repeated measurements: a 

random effect of workstation and fixed effects of survey, floor, remediation, and remediation 

by survey interaction. Remediation was a time-varying covariate in the models. In the 2005 

survey, workstations on only the 6th floor were considered “remediated”. 

† p < 0.05, in comparisons of the remediated and non-remediated workstations for each survey. 

‡ p < 0.1, in comparisons of the remediated and non-remediated workstations for each survey. 

§ Defined as concentration of hydrophilic fungi (CFU/g) divided by that of total fungi (CFU/g) 

in each dust sample; mean hydrophilic fractions were estimated using a generalized linear 

mixed-effects model with a logit link function conditional on the binomial distribution of the 

fraction. 

Health Hazard Evaluation Report 2001-0445-3141 Page 43 
Results (Continued) 

1.0 

0.8 

0.6 

0.4 

0.2 

0.0 

2002 2004 2005 2007 

Survey year 

Figure 11. Box plots for fractions of hydrophilic fungi in total 

fungi concentrations across 4 surveys. Each box plot: an IQR with 

median, upper and lower whiskers: upper and lower boundaries 

(3rd quartile /1st quartile ± 1.5 IQR) 

Association between Exposure to

Environmental Microbial Agents and Occupant 

Health 

Cross-Sectional Analyses of Associations between 

Microbial Exposure and Health 

In data analyses using responses from the case and comparison 

groups (n = 356) selected from the 2001 health questionnaire 

joined with data from the April 2002 environmental evaluation, we 

were able to demonstrate a linear exposure-response relationship 

between fungi, ergosterol, endotoxin, and cat allergen levels with 

the presence of asthma (post-occupancy asthma or epi-asthma) 

or being a respiratory case (Tables 10–11) (Park et al. 2008). 

Hydrophilic and mesophilic fungi showed a much stronger 

relationship with health outcomes than fungi with Aw less than 

0.8. Although cat allergens were mildly associated with health 

outcomes, dog allergen levels showed no association. In general, 

there appeared to be a stronger association with floor dust than 

with chair dust samples. In models with multiple environmental 

parameters, the associations remained for total and hydrophilic 

fungi, and to a lesser extent, ergosterol (data not shown). For a 

more detailed description of associations, please refer to the article 

by Park et al. (2008). 

Page 44 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued)
 Table 10. Association* of floor dust samples with respiratory case status, epi-asthma, 

and post-occupancy current asthma, adjusted for age, sex, race, smoking status, and 

building tenure 

Environmental parameter Odds Ratios 

(95% CI) 

Respiratory case 

Odds Ratios 

(95% CI) 

Epi-asthma 

Odds Ratios 

(95% CI) 

Post-occupancy 

asthma 

Total culturable fungi 1.66† 

(1.19, 2.33) 

1.72† 

(1.21, 2.46) 

1.56‡ 

(0.96, 2.53) 

Fungi with Aw ≥ 0.80 1.66† 

(1.17, 2.38) 

1.69† 

(1.15, 2.47) 

1.72† 

(1.03, 2.88) 

Fungi not classified as Aw ≥ 0.80 1.11 

(0.80, 1.54) 

1.21 

(0.84, 1.72) 

0.80 

(0.47, 1.37) 

Hydrophilic fungi 1.73† 

(1.20, 2.51) 

1.80† 

(1.20, 2.69) 

2.19† 

(1.23, 3.89) 

Ergosterol 1.56† 

(1.13, 2.16) 

1.60† 

(1.13, 2.28) 

1.37 

(0.87, 2.17) 

Endotoxin 1.60† 

(1.09, 2.37) 

1.54† 

(1.01, 2.34) 

1.40 

(0.79, 2.50) 

Cat allergen (Fel d 1) 1.33‡ 

(0.96, 1.83) 

1.35‡ 

(0.95, 1.92) 

1.16 

(0.72, 1.88) 

Dog allergen (Can f 1) 1.18 

(0.85, 1.65) 

1.09 

(0.76, 1.57) 

1.01 

(0.62, 1.65) 

* ORs and 95% CIs were computed based on change of the IQR range in the environmental 

variable. The number of samples for each model varies. Units of the environmental variables are as 

follows: CFU/m2

 for fungi in floor dust; EU/m2 for endotoxin in floor dust; ng/m2 for ergosterol 

in floor dust; and μg/m2 for allergen in floor dust. 

† p < 0.05 

‡ p < 0.10 

Health Hazard Evaluation Report 2001-0445-3141 Page 45 
Results (Continued)
 Table 11. Association* of chair dust samples with respiratory case status, epi-asthma, 

and post-occupancy current asthma, adjusted for age, sex, race, smoking status, and 

building tenure
 

Environmental parameter Odds Ratios 

(95% CI) 

Respiratory case 

Odds Ratios 

(95% CI) 

Epi-asthma 

Odds Ratios 

(95% CI) 

Post-occupancy 

asthma 

Total culturable fungi 1.37† 

(1.02, 1.85) 

1.58† 

(1.13, 2.20) 

1.67† 

(1.07, 2.60) 

Fungi with Aw ≥ 0.80 1.31† 

(1.00, 1.72) 

1.46† 

(1.09, 1.97) 

1.56† 

(1.05, 2.30) 

Fungi not classified as Aw ≥ 0.80 1.09 

(0.76, 1.56) 

1.11 

(0.75, 1.64) 

1.20 

(0.67, 2.18) 

Hydrophilic fungi 1.45† 

(1.07, 1.97) 

1.63† 

(1.16, 2.28) 

1.85† 

(1.19, 2.89) 

Ergosterol 1.38‡ 

(0.98, 1.93) 

1.54† 

(1.05, 2.26) 

1.63‡ 

(0.95, 2.81) 

Endotoxin 1.10 

(0.82, 1.48) 

1.09 

(0.79, 1.52) 

1.15 

(0.71, 1.87) 

Cat allergen 

(Fel d 1) 

1.21 

(0.91, 1.63) 

1.37‡ 

(1.00, 1.88) 

1.55‡ 

(1.00, 2.39) 

Dog allergen 

(Can f 1) 

1.26 

(0.86, 1.83) 

1.20 

(0.78, 1.83) 

1.10 

(0.61, 2.00) 

* ORs and 95% CIs were computed based on change of the IQR range in the environmental 

variable. The number of samples for each model varies. Units of the environmental variables are 

as follows: CFU/m2 for fungi in floor dust and CFU/chair for fungi in chair dust; EU/m2 for 

endotoxin in floor dust and EU/chair for endotoxin in chair dust; ng/m2 for ergosterol in floor 

dust and ng/chair for ergosterol in chair dust; and μg/m2 for allergen in floor dust and μg/chair for 

allergen in chair dust. 

† p < 0.05 

‡ p < 0.10 

To examine the association between the environment and health 

using all 2001 health questionnaire participants (n = 888), we 

classified participants’ exposure as low, medium, or high based 

on their occupied floor and floor-specific means of fungi and 

endotoxin. In these analyses, we were also able to document an 

increased risk of lower respiratory symptoms and rash or itchy 

skin with higher levels of fungi (Figure 12). Other upper and 

non-respiratory symptoms showed little or no association. For 

endotoxin exposure, we found employees in the medium tertile of 

exposure to endotoxin had the greatest amount of risk for some 

lower respiratory symptoms, rhinosinusitis and throat symptoms, 

and some non-respiratory symptoms (Figure 13). Although to 

a lesser extent, employees in the highest tertile group were also 

significantly more likely to have symptoms than the lowest tertile 

group (Park et al. 2006). 

Page 46 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

(LOWER RESPIRATORY)
 

Wheeze_LOW
 

 MEDIUM
 

 HIGH

Chest tightness_LOW

 MEDIUM
 

 HIGH

SOB attacks_LOW

 MEDIUM
 

 HIGH

SOB on level_LOW

 MEDIUM
 

 HIGH

Cough attacks_LOW

 MEDIUM
 

 HIGH

Cough with phlegm_LOW

 MEDIUM
 

 HIGH

Awaken breathing diff_LOW

 MEDIUM
 

 HIGH

(UPPER RESPIRATORY)

Nasal symptoms_LOW
 

 MEDIUM
 

 HIGH

Sinus symptoms_LOW

 MEDIUM
 

 HIGH

Throat Irritations_LOW

 MEDIUM
 

 HIGH

 (OTHER and ASTHMA)

Rash or itchy skin_LOW

 MEDIUM
 

 HIGH

Fever & Chills_LOW

 MEDIUM
 

 HIGH

Headache_LOW

 MEDIUM
 

 HIGH

Post-onset asthma/Med_LOW

 MEDIUM
 

 HIGH

-2 (0.14) -1 (0.37) 0 (1.00) 1 (2.72) 2 (7.39) 3 (20.09) 

Log Odds Ratio (Odds Ratio) 

Figure 12. ORs for BR symptoms in the last 12 months by tertile exposures to fungi, 2001/2002 

surveys. SOB: shortness of breath; Post-onset asthma/Med: post-occupancy onset of asthma with 

use of asthma medications. Fungal Exposure Tertiles (LOW; MEDIUM; HIGH) by Symptoms

Health Hazard Evaluation Report 2001-0445-3141 Page 47 
(LOWER RESPIRATORY) 

Wheeze_LOW 

 MEDIUM 

 HIGH

Chest tightness_LOW

 MEDIUM 

 HIGH

s 

SOB attacks_LOW

m

 MEDIUM 

to

 HIGH

pm

SOB on level_LOW

yS

 MEDIUM 

 y

 HIGH

b) 

Cough attacks_LOW

H

 MEDIUM 

GI

 HIGH

H ;

Cough with phlegm_LOW

UM

 MEDIUM 

DI

 HIGH

E

Awaken diff. breathing_LOW

M ;

 MEDIUM 

W

 HIGH

OL

(UPPER RESPIRATORY)

( s

Nasal symptoms_LOW 

eli

 MEDIUM 

tre

 HIGH

T 

Sinus symptoms_LOW

er

 MEDIUM 

us

 HIGH

op

Throat Irritations_LOW

xE

 MEDIUM 

 ni

 HIGH

x

(OTHER and ASTHMA)

too

Rash or itchy skin_LOW 

dn

 MEDIUM 

E

 HIGH

Fever & Chills_LOW

 MEDIUM 

 HIGH

Headache_LOW

 MEDIUM 

 HIGH

Post-onset asthma/Med_LOW

MEDIUM 

HIGH 

-2 (0.14) -1 (0.37) 0 (1.00) 1 (2.72) 2 (7.39) 3 (20.09) 

Log Odds Ratio (Odds Ratio) 

Figure 13. Odds ratios for BR symptoms in the last 12 months by tertile exposures to endotoxin, 

2001/2002 surveys. SOB: shortness of breath; Post-onset asthma/Med: post-occupancy onset of 

asthma with use of asthma medications. 

Results (Continued) 

Page 48 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

In 2007, we documented an increased risk of BR lower respiratory 

symptoms and post-occupancy asthma among participants in areas 

with high levels of ergosterol, endotoxin, and to a lesser extent, 

total fungi (Interim letter X, available upon request). 

Repeated Measurement Analyses of Associations 

between Exposure and Health 

In the logistic regression model examining the progression of 

BR rhinosinusitis symptoms to BR asthma symptoms or asthma, 

adjusted for 2001 BR rhinosinusitis symptoms, demographics, 

and all three initial 2002 environmental exposures (total fungi, 

endotoxin, and ergosterol), the medium and high tertile exposures 

to fungi in dust significantly increased the odds of developing 

BR asthma symptoms in any one of the follow-up surveys (Table 

12) in an exposure-dependent manner. In this model, the effect 

of initial fungal exposure (measured by culturable fungi in the 

2002 floor dust, but not follow-up survey exposure) on BR asthma 

symptoms in any of the follow-up surveys was independent of the 

effect of 2001 BR rhinosinusitis symptoms, and the odds from 

fungal exposure was higher than that from 2001 BR rhinosinusitis 

symptoms. Exposure to ergosterol or endotoxin in 2002 did 

not increase the odds of developing BR asthma symptoms. To 

increase analytical power, we excluded the non-significant exposure 

variables of ergosterol and endotoxin from the main effect model, 

and the reduced model results showed similar trends to those of 

the full main effect model. In the logistic regression model with 

the four-level interaction variable combining the binary 2001 BR 

rhinosinusitis symptom status with the binary fungal exposure of 

the initial 2002 survey, we found an interaction on an additive 

scale between fungal exposure and BR rhinosinusitis symptoms. 

The odds for developing BR asthma symptoms with the presence 

of both BR rhinosinusitis symptoms and higher fungal exposure 

within the building at the initial survey was much higher (OR = 

7.3, 95% CI = 2.7, 19.7) than the comparison group with higher 

exposure (OR = 3.5, 95% CI = 1.4, 8.8), the BR rhinosinusitis 

symptom group with lower exposure (OR = 2.4, 95% CI = 0.6, 

10.3), or even a summation of these two ORs (Park et al. 2011, 

submitted). 

Health Hazard Evaluation Report 2001-0445-3141 Page 49 
 

Results (Continued) 

Table 12. Increased odds* for developing BR asthma symptoms in any of the follow-up surveys in 

relation to initial 2002 microbial exposures based on measurements in floor dust and interaction 

between the presence of BR rhinosinusitis symptoms and initial fungal exposure 

Independent variables in the model 

(reference group) 

OR (95% CI) 

Main effect model† 

OR (95% CI) 

Reduced model† 

OR (95% CI) 

Interaction model‡ 

BR rhinosinusitis (comparison) 

Culturable fungi (low exposure)

 Medium 

High 

BR rhinosinusitis by fungal exposure 

(comparison/lower exposure)† 

Comparison/higher exposure 

BR rhinosinusitis/lower exposure 

BR rhinosinusitis/higher exposure 

Ergosterol (low exposure) 

Medium 

High 

Endotoxin (low exposure) 

Medium 

High 

2.18 (1.31, 3.64)§ 

3.60 (1.46, 8.88)§ 

4.80 (1.85, 12.44)§ 

– 

– 

– 

0.66 (0.22, 2.00) 

0.69 (0.25, 1.93) 

1.22 (0.47, 3.16) 

0.79 (0.31, 2.01) 

2.14 (1.29, 3.55)§ 

3.08 (1.39, 6.81)§ 

3.45 (1.59, 7.46)§ 

– 

– 

– 

– 

– 

– 

– 

−

–

– 

3.45 (1.36, 8.75)§ 

2.44 (0.58, 10.27) 

7.31 (2.71, 19.70)§ 

– 

– 

– 

– 

* All models were adjusted for year of building occupancy and demographics (age, gender, race, and smoking status). 

† Main effect model included all three exposure variables from the initial environmental survey. Reduced model 

included only culturable fungi as an environmental exposure variable. 

‡ For the interaction model, medium and high tertiles of fungi were grouped into higher exposure for binary fungi 

variable. Then, the four-level categorical variable was created by combining BR rhinosinusitis symptom (presence/
 

comparison) and binary fungi (lower/higher) variables.
 

§ p < 0.05
 

In the analyses using repeated measurements of environmental 

and health data accounting for within-person variability, we found 

significant associations between microbial exposure and respiratory 

health consistent with those from the cross-sectional analyses 

(Table 13). Our trend analyses, controlling for the individual 

respondent’s initial health status in 2001, were based on two 

different types of health outcomes (recent and frequent symptoms 

and less recent symptoms) to examine changes of occupants’ health 

status. The results of these analyses showed that the prevalence 

of symptoms occurring at least once per week in the last 4 weeks 

(recent and frequent symptoms) were generally not improved in 

the survey years since 2001 (Table 14). Prevalences of wheeze, 

asthma symptoms, shortness of breath on exertion, and nasal 

symptoms occurring more than once per week in the last 4 weeks 

tended to increase in subsequent survey years. These findings from 

the repeated measurement analysis were consistent with the trends 

observed in the prevalence analyses of these symptoms over the 

survey years using all four health questionnaire survey participants 

(n = 258) (Figures 3–5). Our symptom severity score analysis 

Page 50 Health Hazard Evaluation Report 2001-0445-3141 
Results (Continued) 

was based on repeated measurements which indicated that the 

individual symptom severity for wheeze and shortness of breath on 

exertion tended to worsen in follow-up surveys. However, fever and 

chills and throat irritation symptom severities improved during the 

6 years of the study (Table 14). 

Table 13. Risks for BR respiratory symptoms by microbial agent, 

based on 2002 exposure* 

BR symptoms OR (95% CI) 

Total fungi 

OR (95% CI) 

Ergosterol 

OR (95% CI) 

Endotoxin 

Wheeze 1.27† 

(1.04, 1.54) 

1.15† 

(1.01, 1.32) 

1.35† 

(1.01, 1.82) 

Chest tightness 1.33† 

(1.10, 1.60) 

1.18† 

(1.03, 1.36) 

1.35† 

(1.02, 1.78) 

Attacks of shortness of 

breath 

1.33† 

(1.10, 1.62) 

1.16† 

(1.02, 1.33) 

1.39† 

(1.04, 1.86) 

Cough attacks 1.26† 

(1.07, 1.49) 

1.18† 

(1.05, 1.31) 

1.11 

(0.87, 1.42) 

Awakened by 

breathing 

difficulty 

1.50† 

(1.10, 2.05) 

1.28‡ 

(1.00, 1.63) 

1.40 

(0.87, 2.24) 

Asthma symptoms 1.30† 

(1.10, 1.54) 

1.19† 

(1.06, 1.33) 

1.32† 

(1.02, 1.69) 

Nasal symptoms 1.20† 

(1.03, 1.40) 

1.17† 

(1.07, 1.28) 

1.35† 

(1.08, 1.69) 

Sinus symptoms 1.08 

(0.91, 1.29) 

1.09 

(0.98, 1.21) 

1.15 

(0.89, 1.50) 

Throat irritation 1.20† 

(1.01, 1.42) 

1.20† 

(1.08, 1.34) 

1.15 

(0.90, 1.47) 

* Estimated from regression models for repeated measurements, after 

controlling for effects of survey, age, gender, race/ethnicity, smoking status, 

and duration of building occupancy. ORs (95% CIs) were computed based on 

the change of the IQR for total culturable fungi (Ln CFU/m2

) (0.84 for 2002 

fungi); ergosterol (Ln ng/m2) (0.46 for 2002 ergosterol); endotoxin (Ln EU/m2) 

(1.66 for 2002 endotoxin). 

† p < 0.05 

‡ p < 0.1 

Health Hazard Evaluation Report 2001-0445-3141 Page 51 
Results (Continued) 

Table 14. Time trends for BR symptoms in the last 4 weeks and changes in 

symptom severity over time 

BR symptoms ORs (95% CI) for BR 

symptoms in last 4 weeks* 

Coefficient for 

symptom severity† 

Wheeze 1.16‡ 

(1.05, 1.29) 

0.023‡ 

(Worsening) 

Chest tightness 1.00 

(0.91, 1.10) 

-0.011 

(No change) 

Attacks of shortness of breath 1.04 

(0.94, 1.16) 

0.002 

(No change) 

Cough attacks 1.05 

(0.97, 1.15) 

-0.0001 

(No change) 

Awakened by breathing difficulty 0.97 

(0.81, 1.16) 

-0.003 

(No change) 

Asthma symptoms 1.08§ 

(1.00, 1.18) 

N/A 

Shortness of breath on exertion 1.17‡ 

(1.06, 1.29) 

0.024‡ 

(Worsening) 

Flu-like achiness 1.00 

(0.90, 1.11) 

-0.008 

(No change) 

Fever and chills 0.97 

(0.83, 1.12) 

-0.015‡ 

(Improving) 

Hypersensitivity pneumonitis-like 

symptoms 

1.06 

(0.96, 1.18) 

N/A 

Nasal symptoms 1.12‡ 

(1.04, 1.20) 

0.015 

(No change) 

Sinus symptoms 1.01 

(0.93, 1.10) 

-0.011 

(No change) 

Throat irritation 0.99 

(0.91, 1.08) 

-0.026‡ 

(Improving) 

* Time trends for BR respiratory symptoms estimated from regression models for repeated 

measurements, including 2002 floor averages of total fungi, ergosterol, and endotoxin 

(continuous), survey year (continuous coded as 1, 4, 5, and 7), age, gender, race/ethnicity, 

smoking status, and duration of building occupancy variables. ORs are shown in one-year 

increments. 

† Symptom score was based on the severity of BR respiratory symptom at the individual level 

and was coded as 0 (no symptom), 1 (12-month symptom only), and 2 (4-week symptom) by 

survey. Coefficients for symptom severity were estimated from regression models for repeated 

measurements, including 2001 floor averages of total fungi, ergosterol, and endotoxin 

(continuous), symptom severity score (continuous), age, gender, race/ethnicity, smoking status, 

and duration of building occupancy variables. If the coefficient is positive and significant, 

it was defined as worsening in symptom severity and if the coefficient was negative and 

significant, it was defined as improving. 

‡ p < 0.05 

§ p < 0.1 

Page 52 Health Hazard Evaluation Report 2001-0445-3141 
disCussion
 

Our four cross-sectional surveys during a 6-year period in this 

office building with a long history of water damage demonstrated 

relationships between exposures to dampness-related agents in the 

building and the adverse effects on occupants’ health from both 

cross-sectional and repeated measurement analyses. Prevalences of 

lower respiratory symptoms and asthma in the building occupants 

were higher compared to national and state data. The substantially 

increased incidence rate of asthma onset after occupancy in the 

building compared to that before occupancy provided strong 

evidence of involvement of the building environment in occupants’ 

respiratory illnesses. The risk of respiratory illnesses in the 

occupants increased in relation to higher levels of microbial agents 

(fungi and endotoxin in floor and chair dust) in the building. 

The respiratory cases relocated in the building had a decrease 

in medication use and sick leave. These findings suggest that 

removing or decreasing occupants’ exposure inside the building is 

important to protect occupants from building-related illnesses. 

Our findings of the association between exposure to dampnessrelated agents and various respiratory symptoms are consistent 

with findings from the 2004 Institute of Medicine report and the 

2009 World Health Organization guidelines, which conclude that 

there is sufficient evidence of an association between damp indoor 

environments and upper respiratory symptoms, wheeze, cough, 

and exacerbation of asthma symptoms (Institute of Medicine 2004, 

World Health Organization 2009). In addition, the World Health 

Organization guidelines further concluded that there is sufficient 

evidence of an association between exposure to dampness-related 

agents and the development of asthma, which is also consistent 

with the findings from our evaluations of the building. The World 

Health Organization guidelines reported that there is clinical 

evidence to support that mold and other microbial measures can 

increase the risk of developing hypersensitivity pneumonitis and 

chronic rhinosinusitis (World Health Organization 2009). This 

conclusion is also consistent with our findings on the occurrence 

of hypersensitivity pneumonitis and rhinosinusitis symptoms 

related to this damp building. 

During the 6 years we studied the building, building management 

placed much effort on repairing water leaks and replacing 

damaged building materials, including carpets and dry wall. 

Indeed, prevalences of symptoms among persons who occupied 

the building after major remediation was completed in 2004 were 

consistently lower when compared to longer term employees (those 

who occupied the building prior to 2004). This may indicate 

some positive effects of remediation on lowering the prevalence 

Health Hazard Evaluation Report 2001-0445-3141 Page 53 
disCussion (Continued) 

of symptoms among new employees. This positive remediation 

effect was also observed in the analyses of new onset of diseases. 

We found the number of diagnoses of post-occupancy asthma, 

sarcoidosis, and hypersensitivity pneumonitis cases appeared to 

be decreasing by 2007. By the time our survey ended in October 

2007, two post-occupancy asthma diagnoses, two hypersensitivity 

pneumonitis cases, and no sarcoidosis cases had been reported for 

that year. This is considerably lower than between the years 2000 

and 2002 before the major remediation, when cases of asthma, 

hypersensitivity pneumonitis, and sarcoidosis reached their peak. 

However, this decrease in the number of cases reported could have 

been due to the study ending before the end of the year in 2007 

and the lack of follow-up time. The decrease in new diagnosis of 

post-occupancy asthma cases was also confirmed by the incidence 

density analysis on the 2007 survey data which takes the amount 

of follow-up time into account. However, even though there was 

a decline, the rate of post-occupancy asthma diagnosed between 

2004 and 2007 was still 4.1 times higher than the pre-occupancy 

adult-onset asthma rate. Our other repeated measurement analyses 

examining changes of BR symptom severity (no symptom, less 

recent symptoms, or recent and frequent symptoms) showed 

alleviation in symptom severity for acute symptoms such as fever/ 

chills and throat irritation symptoms, which may also indicate a 

remediation effect. 

On the other hand, consistently higher symptom prevalence 

in longer term employees even after the major remediation 

was completed implies that respiratory symptoms in those with 

chronic exposure to the damp building environment may not 

be easily improved. In this building population, the majority 

(79%) of participants occupied the building before 2001 and 

this subpopulation appeared to have contributed to the overall 

increased burden of BR respiratory illnesses among building 

occupants. This persistently high prevalence contributed by the 

longer term employees was also reflected by our findings in the 

repeated measurement analysis that risks of wheeze or shortness of 

breath on exertion significantly increased and that the severity of 

those symptoms also significantly increased over the survey years. 

Another repeated measurement analysis of symptoms and objective 

medical tests also indicated that a subgroup of the longer term 

employees (97 employees who participated in both 2002 and 2005 

medical surveys) did not generally show improvement in respiratory 

health, as reflected in symptom scores, overall medication use, 

spirometry abnormalities, or sick leave. In addition, our analysis 

on the progression of upper to lower respiratory symptoms among 

another subgroup of longer term employees showed that the 

Page 54 Health Hazard Evaluation Report 2001-0445-3141 
disCussion (Continued) 

building occupants who reported BR rhinosinusitis symptoms 

in the initial 2001 survey were about twice as likely to develop 

asthma or BR asthma symptoms in subsequent survey years despite 

remediation. The effect of BR rhinosinusitis symptoms on asthma 

development was independent of that of mold or other dampnessrelated exposures. This finding may imply that once nasal and 

sinus symptoms develop due to exposure to dampness-related 

agents in building environments, the symptoms tend to progress 

to more severe and chronic illnesses such as asthma symptoms or 

asthma. Furthermore, the risk was much increased if those with 

rhinosinusitis symptoms were exposed to higher fungal levels 

or dampness-related agents in the building. These findings may 

indicate that controlling exposure through remediation during the 

early stages of water damage in a building is important to prevent 

onset of upper respiratory illnesses and their progression to chronic 

lower respiratory illnesses. 

In many instances of water damage in modern buildings, finding 

sources of water leaks and damage at an early stage is difficult 

unless the building is being routinely and carefully monitored. In 

water-damaged buildings with hidden sources, occupant reports 

of health symptoms provide valuable information on the building 

environment and the occupants’ potential exposure to buildingrelated contaminants. If building management cannot implement 

remediation immediately after sources of water damages are 

identified, relocation of affected occupants should be seriously 

considered. Our study demonstrated substantial improvement in 

the health of relocated respiratory cases by the reported decrease 

in medication use and sick leave. Therefore, close communication 

between management, physicians, and occupants in relation 

to building-related health symptoms and the environmental 

conditions of occupied spaces is crucial to prevent occupant 

illnesses due to dampness-related exposures in buildings. 

Although there were some indications of improvement in 

BR symptoms among the occupants, we generally found no 

improvement in risks and severity for many of the respiratory and 

non-respiratory symptoms as discussed earlier. This mixed result 

of remediation effects on occupants’ health might be explained 

by partially successful remediation. Our repeated measurement 

analyses on environmental microbial agents indicated that the 

major remediation completed between 2002 and early 2004 had 

significantly decreased microbial levels in remediated workstations 

in 2004 and to a lesser degree in 2005, but not in 2007. The 

remediation effect in the 2004 survey was most evident as shown 

by the substantial decrease in the proportion of hydrophilic 

Health Hazard Evaluation Report 2001-0445-3141 Page 55 
disCussion (Continued) 

fungi to total fungi, but the proportion started to increase in 

2005, and further increased in 2007 where both the level and 

the proportion were eventually higher than that in 2002. Rates 

of lower respiratory symptoms and asthma remained elevated 

when compared to national and state data in all follow-up surveys 

conducted after the major remediation. Indeed, after the major 

remediation was completed in early 2004, ongoing water leaks 

from exterior windows on the upper floors (16–19) and leaks in 

the corner offices on the18th floor located directly below corner 

balconies of the 19th floor, had been documented by a consultant 

(Silver Petrucelli & Associates, Inc.). Another unpublished 

consultant report (Turner Building Science, LLC) noted that 

the building envelope was constructed according to a pre-1987 

design: the envelope relied primarily on brick sealants between the 

window assembly and the brick veneer to keep wind-driven rain 

out of the structure. This older design does not have continuous 

drainage planes behind the brick veneer, which eventually leads 

to penetration of rainwater into the building. These findings 

emphasize that complete building diagnosis, including building 

inspections for water incursion to ascertain water sources, is 

essential because incomplete remediation eventually allows 

persistent water leaks. Recurring microbial proliferation and 

dissemination even after remediation is likely to adversely affect 

occupants with building-related illnesses and produce new cases. 

Studies have indicated that workers with occupational asthma 

who continue to be exposed to the causative agent generally do 

not improve and may even deteriorate (Chan-Yeung and Malo 

1993), and that those with shorter exposure durations tended 

to have higher rates of recovery (Rachiotis et al. 2007). However, 

exposure cessation is not always curative since many workers with 

occupational asthma can be left with permanent asthma symptoms 

and lung function abnormalities (Chan-Yeung and Malo 1993). A 

recent review article concluded that exposure cessation has been 

found to be more likely than exposure reduction to result in some 

degree of improvement in asthma symptoms and lung function 

abnormalities (Vandenplas et al. 2011). In a study which examines 

the effect of dampness remediation on students’ health, it was 

found that remediation may be effective in terms of preventing 

new illness, but not eliminating symptoms in previously affected 

occupants (Haverinen-Shaughnessy et al. 2004). Our findings from 

the multiple cross-sectional evaluations are consistent with the 

literature in that affected occupants with long histories of exposure 

to increased levels of microbial or other dampness-related agents 

did not improve as a group in their respiratory symptoms, especially 

chronic ones such as wheeze and shortness of breath on exertion, 

Page 56 Health Hazard Evaluation Report 2001-0445-3141 
disCussion (Continued) 

regardless of remediation. Overall, our findings emphasize that 

early detection of various signs of dampness and mold through 

routine and thorough inspection is essential; however, once 

the building is damaged by moisture incursion, immediate and 

complete remediation is vital for protecting occupants’ health from 

potential dampness-related exposure. 

There are limitations to this work. Our repeated measurement 

analysis on the progression of upper to lower respiratory symptoms 

and asthma was based on multiple cross-sectional surveys of 

participants. Occupants who participated in 2004 or 2005 but 

not in 2007, and who did not report building-related asthma 

symptoms or asthma diagnosis in the earlier surveys, might have 

developed the symptoms or had the diagnosis since their last survey 

that we did not ascertain in 2007. Therefore, there may be an 

underestimation in identifying building-related asthma symptoms 

or diagnoses reported in the follow-up surveys. However, this 

underestimation is not likely to change our conclusions because we 

obtained similar results when we analyzed only respondents who 

participated in all four surveys. The healthy worker effect might 

have also resulted in an underestimation of health outcomes in 

the follow-up surveys because some of the occupants with buildingrelated respiratory disease had left employment or relocated to 

facilities outside the building before the follow-up survey. Another 

limitation in our repeated measurement analysis is the loss of 30% 

of the initial 2001 respondents in the follow-up surveys. However, 

the demographics and prevalences of rhinosinusitis symptoms 

were similar among non-participants and participants in follow-up, 

which may imply minimal participation bias. 

In our surveys we were unable to characterize personal workstation 

dust exposure for each health questionnaire participant. We 

assigned exposure based on floor-specific means of the microbial 

measurements in some epidemiologic analyses of this report, 

which might have produced exposure misclassification in some 

occupants. However, unless selection of sampling locations within 

the floors was biased, assigning exposure to individuals based on 

their floor and using tertiles of floor-specific means was not likely 

to be influenced by individual health response, implying that the 

potential exposure misclassification is likely to be non-differential, 

if any. Sampling locations on each floor appeared to be evenly 

distributed throughout all spaces within the floor in all four 

surveys including 2002 and 2004 when the samples were collected 

from workstations of 2001 participants with and without lower 

respiratory symptoms or diagnoses, implying that the floor-specific 

means are a good representation of average exposure of occupants 

Health Hazard Evaluation Report 2001-0445-3141 Page 57 
disCussion (Continued) 

within specific floors. Misclassification of exposure which is 

independent of participants’ health generally decreases the strength 

of association. Even with this potential attenuation, we were able 

to demonstrate associations between exposure and health. 

ConClusions
 From our study of this building over a 6 year period, we 

documented an excess of respiratory illnesses in the building. 

Physician-diagnosed asthma, wheeze, attacks of shortness of 

breath, and nasal and eye symptoms were significantly higher 

when compared to national and state data. However, the newonset of diseases such as asthma, hypersensitivity pneumonitis, 

and sarcoidosis have in general been declining since 2000 or 

2001. In addition, persons who have been in the building for 

a shorter period of time (2004 or later) appear to have a lower 

prevalence of respiratory and non-respiratory symptoms. Despite 

some improvement, the longer term employees (hired before 

2004) still showed no overall improvement in their health and 

even had increased risks of BR respiratory symptoms and postoccupancy asthma. They also had a higher risk of developing BR 

asthma symptoms if they had already developed BR nasal or sinus 

symptoms and remained in the building with relatively higher 

exposures to mold or other dampness-related agents. Although 

there had been continuous efforts to remediate water damage 

during the study period, it appeared that the initial success 

demonstrated in 2004 was not maintained. After three years, the 

remediation effect on the building environment and occupants’ 

health was minimal. This may be due to the effects of longer-term 

employees on the burden of disease among building occupants, 

only partially successful remediation, or a combination of the two. 

Water damage in this building is a public health problem with a 

substantial burden of disease associated with the building. There 

is a potential for ongoing water incursion due to the pre-1987 

building design which did not include a continuous drainage 

plane behind the brick veneer. Continued attention to finding 

and remediating sources of water incursion is essential in such 

circumstances. Occupants should be informed of continued 

environmental and health issues, have the option of medical 

surveillance, and be relocated to dry work spaces at the onset 

of symptoms to avoid potentially long-term chronic respiratory 

disease. 

Page 58 Health Hazard Evaluation Report 2001-0445-3141 
ReCommendAtions
 On the basis of these findings from our evaluations and data 

analyses, we recommend the following: 

1.	 Continue a routine maintenance program for evaluation 

and repair of water damage in the building, including 

regular observational assessment of water stains, mold 

growth, mold odors, and dampness, and systematic 

evaluation of window leaks, roof leaks, and functionality of 

exterior walls. 

2.	 Continue to communicate with occupants regarding indoor 

environmental complaints (water damage, water stains, 

indoor air quality, etc.) and BR health complaints. 

3.	 Initiate a surveillance program to monitor occupants’ 

symptoms and new onset of possible building-related 

illnesses, with appropriate clinical referral for diagnostic 

tests, follow-up, and consideration of need for relocation. 

4.	 For those persons with BR symptoms or illness, remove 

dampness problems and sources of microbial contamination 

from their work environment, or relocate to another area of 

the building or a different building. 

5.	 Continue to practice daily or routine cleaning and 

housekeeping protocols, including HEPA vacuuming, to 

more efficiently remove potential microbial agents or other 

contaminants, and to minimize accumulation of dust in 

floor carpet and other surfaces. 

6.	 Reconsider the following recommendation as given in 

Turner Building Science, LLC report from December 

2005: “Evaluate a Redesign of the Exterior Envelope of 

the Facility to More Permanently Stop Rain Intrusion with 

a Redundant, Continuous Drainage Plane/Air Barrier/ 

Insulation Layer System, Installed from the Interior.” 

7.	 Advise employees of the availability of this report, and place 

the report on the website as was done with the interim 

reports. 

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Page 62 Health Hazard Evaluation Report 2001-0445-3141 
ACknowledgements And 

AvAilAbility of RepoRt 

The Respiratory Disease Hazard Evaluation and Technical 

Assistance Program of NIOSH conducts field investigations of 

possible health hazards in the workplace. These investigations 

are conducted under the authority of Section 20(a)(6) of the 

Occupational Safety and Health Act of 1970, 29 U.S.C. 669(a)(6), 

or Section 501(a)(11) of the Federal Mine Safety and Health Act 

of 1977, 30 U.S.C. 951(a)(11), which authorizes the Secretary of 

Health and Human Services, following a written request from any 

employers or authorized representative of employees, to determine 

whether any substance normally found in the place of employment 

has potentially toxic effects in such concentrations as used or 

found. 

Mention of any company or product does not constitute 

endorsement by NIOSH. In addition, citations to websites 

external to NIOSH do not constitute NIOSH endorsement of 

the sponsoring organizations or their programs or products. 

Furthermore, NIOSH is not responsible for the content of these 

websites. All Web addresses referenced in this document were 

accessible as of the publication date. 

The Respiratory Disease Hazard Evaluation and Technical 

Assistance Program also provides, upon request, technical and 

consultative assistance to federal, state, and local agencies; labor; 

industry; and other groups or individuals to control occupational 

health hazards and to prevent related trauma and disease. 

This report was prepared by Ju-Hyeong Park, Sandra K. White, 

Sook Ja Cho, and Jean M. Cox-Ganser of the Division of 

Respiratory Disease Studies. Industrial hygiene field assistance was 

provided by Randy Boylstein, Michael Beaty, Kyoo T. Choe, Everett 

Elliot, Thomas Jefferson, Greg Kullman, Chris Piaciatelli, Terri 

Pearce, Carol Rao, and Dan Yereb. Medical field assistance was 

provided by Muge Akpinar-Elci, Lisa Benaise, Dee Cress, Andrea 

Driscoll, Everett Elliot, Diana Freeland, Amber Harton, Kenneth 

Hilsbos, Chris Hoffman, Yulia Iossifova, Michelle Martin, Ray 

Petsko, Marty Pflock, Betsy Shogren, David Spainhour, Marcia 

Stanton, Kimberly Jo Stemple, Eileen Storey, Jim Taylor, and 

Brian Tift. Statistical support was provided by Nicole Edwards 

and Rebecca Jones. Desktop publishing was performed by Tia 

McClelland. 

Health Hazard Evaluation Report 2001-0445-3141 Page 63 
 

 

ACknowledgements And 

AvAilAbility of RepoRt 

(Continued)	 Copies of this report have been sent to employee and management 

representatives at the Connecticut Agencies housed in the 

building, the Unions represented in the building, and the OSHA 

Regional Office. This report is not copyrighted and may be freely 

reproduced. The report may be viewed and printed at www.cdc. 

gov/niosh/hhe/. Copies may be purchased from the National 

Technical Information Service (NTIS) at 5825 Port Royal Road, 

Springfield, Virginia 22161. 

Page 64	 Health Hazard Evaluation Report 2001-0445-3141 
Below is a recommended citation for this report:

NIOSH [2011]. Health Hazard Evaluation Report: Evaluation of Respiratory Health 

among Employees in a Water-Damaged Office Building–Connecticut. Morgantown, 

WV: U.S. Department of Health and Human Services, Public Health Service, 

Centers for Disease Control and Prevention, National Institutute for Occupational 

Safety and Health, NIOSH HETA No. 2001-0445-3141

To receive NIOSH documents or information about 

occupational safety and health topics contact NIOSH at:

1-800-35-NIOSH (1-800-356-4674)

Fax: 1-513-533-8573

E-mail: pubstaft@cdc.gov

or visit the NIOSH web site at:

http://www.cdc.gov/niosh/hhe

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Safety and health at work for all people

through research and prevention.

 National Institute for Occupational 

Safety and Health