Content uploaded by Peder Wolkoff
Author content
All content in this area was uploaded by Peder Wolkoff on Mar 04, 2020
Content may be subject to copyright.
Content uploaded by Peder Wolkoff
Author content
All content in this area was uploaded by Peder Wolkoff on Apr 19, 2018
Content may be subject to copyright.
Content uploaded by Peder Wolkoff
Author content
All content in this area was uploaded by Peder Wolkoff on Feb 28, 2018
Content may be subject to copyright.
Contents lists available at ScienceDirect
International Journal of Hygiene and
Environmental Health
journal homepage: www.elsevier.com/locate/ijheh
Review
Indoor air humidity, air quality, and health –An overview
Peder Wolkoff
National Research Centre for the Working Environment, NRCWE, Lersø Parkallé 105, Copenhagen Ø, Denmark
ARTICLE INFO
Keywords:
Air quality
Airways
Eyes
Humidity
Influenza virus
Sensory irritation
Sleep quality
ABSTRACT
There is a long-standing dispute about indoor air humidity and perceived indoor air quality (IAQ) and associated
health effects. Complaints about sensory irritation in eyes and upper airways are generally among top-two
symptoms together with the perception “dry air”in office environments. This calls for an integrated analysis of
indoor air humidity and eye and airway health effects. This overview has reviewed the literature about the
effects of extended exposure to low humidity on perceived IAQ, sensory irritation symptoms in eyes and airways,
work performance, sleep quality, virus survival, and voice disruption. Elevation of the indoor air humidity may
positively impact perceived IAQ, eye symptomatology, and possibly work performance in the office environ-
ment; however, mice inhalation studies do not show exacerbation of sensory irritation in the airways by low
humidity. Elevated humidified indoor air appears to reduce nasal symptoms in patients suffering from ob-
structive apnea syndrome, while no clear improvement on voice production has been identified, except for those
with vocal fatigue. Both low and high RH, and perhaps even better absolute humidity (water vapor), favors
transmission and survival of influenza virus in many studies, but the relationship between temperature, hu-
midity, and the virus and aerosol dynamics is complex, which in the end depends on the individual virus type
and its physical/chemical properties. Dry and humid air perception continues to be reported in offices and in
residential areas, despite the IAQ parameter “dry air”(or “wet/humid air”) is semantically misleading, because a
sensory organ for humidity is non-existing in humans. This IAQ parameter appears to reflect different percep-
tions among other odor, dustiness, and possibly exacerbated by desiccation effect of low air humidity.
It is salient to distinguish between indoor air humidity (relative or absolute) near the breathing and ocular
zone and phenomena caused by moisture-damage of the building construction and emissions therefrom. Further,
residential versus public environments should be considered as separate entities with different characteristics
and demands of humidity. Research is needed about particle, bacteria and virus dynamics indoors for im-
provement of quality of life and with more focus on the impact of absolute humidity. “Dry (or wet) air”should be
redefined to become a meaningful IAQ descriptor.
1. Introduction
Yaglou (1937) concluded that “Artificial humidification, about
which so much is heard on connection with winter air conditioning,
was shown in the first part of this paper to be relatively unimportant
from the standpoint of comfort and, so far is known, not essential from
the standpoint of health. While a relative humidity of between 40 and
60 percent would probably be more normal and perhaps more healthful
than between 20 and 30 percent, it is practically impossible to maintain
this high range in cold weather because excessive condensation and
freezing on the windows and sometimes inside the exposed walls”.
Indoor air humidity, in terms of perceived dry air (dryness) and
potentially associated health effects is an important parameter (relative
(RH) or absolute (AH)) both in the aircraft and office environment. A
long-standing dispute continues about the health relevance of RH and
the cause(s) of perceived “dry air”, a very common and abundant
complaint about perceived indoor air quality (IAQ)inoffice-like en-
vironments. Further to this, causation of perceived sensory reactions in
eyes and upper airways, among top-two reported symptoms in offices,
continue to be a puzzle, despite several identified risk factors that in-
fluence the development of eye symptoms have been identified
(Wolkoff, 2017); the risks of symptoms in the upper airways remain
largely unexplained. Furthermore, there is an increasing recognition of
the impact of humidity, e.g. on virus survival and transmission and
sleep quality, regarding derivation of a safe limit for indoor air hu-
midity (Derby et al., 2016).
Nagda and Hodgson (2001) reviewed the indoor air literature and
concluded that slightly elevated RH would have a beneficial effect on
perceived IAQ; in part based on the conclusion that experimental out-
comes appeared to be strongly dependent upon the experimental
https://doi.org/10.1016/j.ijheh.2018.01.015
Received 17 October 2017; Received in revised form 28 December 2017; Accepted 29 January 2018
E-mail address: pwo@nrcwe.dk.
International Journal of Hygiene and Environmental Health 221 (2018) 376–390
1438-4639/ © 2018 The Author. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
T
design. A conclusion that was further supported by Wolkoffand
Kjærgaard (2007). It was unclear, however, whether the conclusion
reached by Nagda and Hodgson (2001) would include typical sensory
and CNS-related symptoms as commonly encountered in office en-
vironments. Contrary to this, the pollutant hypothesis was reintroduced
partially based on short-term assessments of the emissions from
building materials (Fang et al., 1999) and by Sundell and Lindvall
(1993) and Fang et al. (2004). These authors concluded that indoor air
pollutants, like volatile organic compounds (VOCs), were the most
likely cause of reported dry air by exposure to sensory irritants. Fur-
thermore, it was concluded that high RH as well as high temperature
were detrimental to the immediately perceived IAQ (a snapshot of
perception) by “sniffing”the emission from building materials (Fang
et al., 1998). In that context, Fanger (2000) concluded that IAQ should
be perceived as “dry and cool”in office environments, i.e. low RH and
not too warm. Sun et al. (2009) and Qian et al. (2016) further ad-
vocated this stating that the perception of dry air is more likely related
to “sensory irritants”, despite lack of a clear scientific rationale.
Thus, there is a need for a balanced and integrated analysis of the
impact of indoor air humidity on associated health effects as opposed to
the well-known problems associated with moisture-damaged buildings
(World Health Organization, 2009). As pointed out the relationship
between health, indoor air humidity and pollution is complex and re-
mains a challenge (Davis et al., 2016a;Derby et al., 2016). Thus, the
focus of this overview is effects in the public domain of perceived IAQ,
sensory irritation in eyes and airways, work performance, infection by
virus, sleep quality, and the voice.
2. Method
This overview integrates and analyzes studies about how “ex-
tended”exposure to low relative (absolute) humidity impacts health,
IAQ, work performance, sensory effects in the eyes and airways (sen-
sory symptoms), transmission and survival of influenza virus, sleep
quality, and the vocal cord. Searches in PubMed and Google Scholar
were carried out for “humidity”in combination with: “airways”,
“asthma”,“eyes”,“indoor air quality”,“particles”,“pungency”,
mucociliary clearance”,“sensory irritation”,“throat irritation”,“ocular
surface”,“sleep quality”, and “voice or vocal cords”, and combined
with own selection of literature compiled during the last decade up to
September 2017, cf. Arundel et al. (1986),Derby et al. (2016),Nagda
and Hodgson (2001),Wolkoffand Kjærgaard (2007). Health effects of
moisture damage (dampness) of construction products and mold-re-
lated issues (e.g. microbiological contaminants) and dust mites are
excluded from this overview, cf. Hurraß et al. (2017) and World Health
Organization (2009).
2.1. Absolute and relative humidity definition
Humidity is usually measured by a hygrometer and reported as re-
lative −% water vapor in the room air relative to the total amount of
vapor in the same room air may contain at given temperature; absolute
humidity amounts the water in grams per kg of air (g/kg) at a defined
pressure. Thus, indoor AH appears to correlate better with outdoor AH
than outdoor and indoor RH in some regions, but not in others, in part
depending on season, building style, and ventilation (Nguyen et al.,
2014;Zhang and Yoshino, 2010).
3. Results of overview
3.1. Offices –symptoms, perception of IAQ (VOCs, particles), and work
performance
3.1.1. Symptoms in offices
Irritation in eyes and upper airways are among top-two reported
symptoms in office questionnaire studies (Brightman et al., 2008;
Bluyssen et al., 2016;Wolkoff, 2013). There are minor differences be-
tween the studies which in part reflect the recall period, usually one
symptom per week during the last four weeks. The reported prevalence
is generally from 20 to 40%.
Several questionnaire studies in offices have shown associations
between low RH (5–30%) and increased prevalence of complaints about
perceived dry and stuffy air and sensory irritation of the eyes and upper
airways, see Table 1. However, many intervention studies have shown
Table 1
Studies in office environments, homes, schools, and hospitals.
Authors
Environment
Study Observation
Angelon-Gaetz et al. (2016)
Schools
Teachers (n = 122) reported daily symptoms in 4–12 weeks diaries. Modest, but not significant, increase in respiratory (asthma-like)
symptoms over 5 days, both at low (< 30%) and high RH (> 50%) in
comparison to referent teachers (30–50% RH). No effects of RH on
cold/allergy symptoms.
Azuma et al. (2015, 2017) Offices - Workers (n = 3335) in 320 offices responded to questionnaire. Both studies showed strong correlation between perceived air dryness
and report of eye irritation.
- Workers (n = 3024) in 489 offices responded to questionnaire. General symptoms were also associated with perceived humidity in
the summer season.
Bakke et al. (2007,2008) Offices Four university buildings, 2 complaint and 2 control buildings.
Questionnaire and examination of the precorneal tear film (PTF)
stability, nasal patency and inflammatory markers in nasal lavage
fluid in university staffmembers.
Stuffy or dry air was significantly associated with low RH (15–35%
RH). Otherwise no significant exposure differences between complaint
and control buildings and no significant difference in objective
signs.PTF stability (NBUT/SBUT) was improved at higher RH and
perception of air dryness was reduced.
Brasche et al. (2005) Offices Data from office workers (n = 814) No clear conclusion about RH and reported eye symptoms or PTF
stability. Indication that high RH might be protective, and particles
associated with epithelial damage of the PTF.
Hashiguchi et al. (2008) Hospital Temperature and RH measured for 3 months in hospital in
sickrooms and wardens during winter. Symptoms and comfort was
reported once a week by staff(n = 45) and patients (n = 36).
Humidifiers were installed after 2 months in half of the rooms.
Humidification from 33 to 44% RH, on average, resulted in decrease
of thermal discomfort and perceived air dryness among the staff, but
not among the patients.
Lindgren et al. (2007) Aircraft Cabin attendants (n = 58) and pilots (n = 22).
Double blinded 3–10% increase of RH by ceramic humidifier during
long-haul flights.
Significantly lower concentration of respirable particles at elevated
RH from 6 to 1 μg/m
3
; similar observation for mold and bacteria.
Cabin air quality significantly improved at elevated RH by being
perceived less dry and fresher.
(continued on next page)
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
377
that an increase of RH may alleviate the perception of dry air and
symptoms of dry eyes and upper airways, i.e. the longer-term IAQ re-
duces the symptom reporting; for example, see Hashiguchi et al. (2008)
and other intervention studies shown in Table 1.
3.1.2. Perceived air quality
Perceived IAQ is an umbrella of reported descriptors like tempera-
ture, draft, odor/smell, stuffy air, and dry and wet (humid) air, and
where “dry air”is a common and among the most abundant, e.g.
Bluyssen et al. (2016). The perception of “dry air”can be associated
with mucous membrane irritation of the eyes (e.g. dry eyes) and upper
airways in presence of strong sensory irritants (Doty et al., 2004), which
is an important component included in the classic “sick-building syn-
drome”in non-industrialized buildings. For further discussion of the
semantic validity of this terminology, see Wolkoff(2013).
There is some inconsistency about the perceived IAQ by humidifi-
cation. Thus, the immediately (snapshot) perceived IAQ, not to be
confused with symptoms, appears more acceptable in laboratory set-
tings at low RH and low temperature from the assessment of VOC
emission from building materials (Fang et al., 1998). However, the
thermodynamic condition (i.e. the influence of temperature and RH
(Zhou et al., 2017)) and altered VOC emission profiles influences the
Table 1 (continued)
Authors
Environment
Study Observation
Lukcso et al. (2016) Offices Office workers (n = 7637; response rate 49%) in 12 buildings.
Subset wore personal sampling equipment and underwent medical
examination. Symptoms experienced over the last 4 weeks.
Low RH was significantly associated with lower respiratory and sick-
building syndrome-type symptoms, thus suggesting that low RH may
exacerbate upper and lower airway symptoms.
Nordström et al. (1994) Hospital Blinded steam air humidification to 40–45% RH in two units and
compared with two control units of 25–35% RH in a 4 months
period. Air quality and symptoms were reported before and after
intervention in hospital staff(n = 104).
Significant decrease of perceived air dryness and airway symptoms.
Weekly sensation of air dryness was 24% in humidified units contrary
to 73% in the non-humidified units. Perceived IAQ was unchanged in
control unit.
Norbäck et al. (2000) See also
Nordström et al. (1994)
Hospital
Longitudinal 6 weeks study with blinded steam humidification in
hospital with two units with independent ventilation systems,
outside of pollen season. Staff(n = 26, 100% female; 14 in
humidity group and 12 in non-humidity control group) were
investigated before and after humidification applied in one of the
units for a period of 6 weeks. Questionnaire and medical
examination before and after.
The perception of air dryness was reduced significantly (p = 0.04)
from 73 to 36% in the humidification unit by increase of RH from 35
to 43%, while only slightly reduced in the control group (90–81%).
Perception of dustiness and stuffy air remained unchanged.
No changes in the PTF stability (SBUT), nasal patency (rhinometry),
and inflammatory markers in nasal lavage fluid.
Cannot be excluded that outdoor RH may have influenced, also, although
exposed subjects and controls were investigated on the same days.
Reinikainen et al. (1992) Offices Office workers (n = 290) and cross-over trial, in two wings. Slight
increase of temperature during humidification.
Dryness symptom score (dryness, irritation or itching of the skin and
eyes; dry throat and nose) was significantly smaller (p < 0.01) during
humidification (30–40% RH) compared with the non-humidification
phase (20–30% RH). However, the perception of stuffy air increased
significantly during humidification, which also included unpleasant
odor and dustiness perceptions (not significant).
Reinikainen et al. (1997) Offices Steam humidification up to 30–40% RH compared with non-
humidified units.
Humidification caused a decrease of the perceived IAQ, strongest
among women.
Cross-over trial, use of naïve panel (n = 20) to assess the perceived
IAQ, weekly.
Reinikainen and Jaakkola (2001)
Offices
Same office workers as in 1992 study. Cross-over trial in two wings.
One wing humidified and the other non-humidified for one week
(constant temperature), then switch for a total of 6 weeks. Daily
questionnaire.
High temperature conditions increased dryness symptoms and sick-
building syndrome symptoms during non-humidified conditions.
Increase of RH from about 25–35% resulted in fewer sick-building
syndrome symptom complaints.
Synthesis of studies: high temperature conditions increased sick-
building syndrome symptoms in 4 out of 7 studies; high temperature
resulted in an increase of perceived dryness. Humidification
reportedly decreased sick-building syndrome symptoms or dryness in
5 out of 11 studies and in 3 studies an increase.
Present study showed lower sick-building syndrome symptoms than in
non-humidified conditions and alleviation of perceived dryness during
humidification. Dryness increased more acutely under non-humidified
conditions.
Reinikainen and Jaakkola (2003)
Offices
Office workers (n = 368; 71%) returned baseline questionnaire and
diaries with information about symptoms or perceptions; 342
diaries from non-humidified (25–26% RH) and 233 from humidified
conditions (21–49% RH). Temperature from 21 to 26 °C.
Eye dryness was alleviated, but not significant. Humidification
decreased nasal dryness. High temperature increased nasal congestion
significantly (especially for AH). Odor perception increased at elevated
RH; slightly stronger for AH. “Stuffiness seemed to be associated with
humidification”. Humidification alleviated nasal congestion.
Sato et al. (2003) Factory Comparison workers (n =12) in ultra-low RH (2.5%) with workers
(n = 143) at normal RH.
33% versus 18% reported eye symptoms in ultra-dry and normal RH,
respectively, but not significantly. Skin complaints were significantly
higher at ultra-low RH.
Singh and Jaiswal (2013)
Cochrane review
Only two selected double-blind studies. Conclusion: Little (scanty evidence) benefit from use of
dehumidification by use of mechanical devices on the clinical status of
asthma patients’sensitive to house dust mites.
Wiik (2011) Offices Comparison of responses from office workers (n = 484) and green
house workers (n = 21).
Deteriorated productivity in offices at dry conditions based on
calculating the “indoor productivity index”from questionnaire data.
Wright et al. (2009) Homes Double-blind placebo control (ventilation) study; intervention in
about half of the homes of adults (n = 120) with asthma (dust
mite): 54 active with mechanical-heat-recovery-ventilation and 47
placebo. RH went from 45% to 21%.
Carpets were steam-cleaned, new bedding and mattress before
activation of the mechanical heat-recovery-ventilation. The addition
of mechanical-heat-recovery-ventilation to house dust mite
eradication strategies did not reduce mite allergen levels, but did
improve evening peak expiratory flow.
AH = absolute humidity. NBUT = non-destructive break-up time of PTF (same as SBUT). RH = relative humidity. SBUT = subjective break-up time of PTF. PTF = precorneal (eye) tear
film.
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
378
perception of IAQ (Cain et al., 2002;Fang et al., 1998). For instance,
the emission profile of polar VOCs from building materials may alter
markedly by increase of the RH, e.g. Fang et al. (1999),Fechter et al.
(2006),Huang et al. (2016),Markowicz and Larsson (2015),Wolkoff
(1998), but also the temperature including competitive adsorption
mechanisms and water solubility (Zhou et al., 2017).
The immediate perception of odor and “stuffy air”increased slightly
upon increase of RH in offices (Reinikainen et al., 1997;Reinikainen
and Jaakkola, 2003), see Table 1. Thus, the perceived stuffiness may, in
part, be caused by the altered VOC (odor) emission profile combined
with the thermodynamic effect. However, at the same time, alteration
of the inhalable particle chemical composition, the deposition and re-
suspension that occur from surfaces may differ at different RH, see
below. This is especially for particles that predominantly deposit in the
nostrils and upper airways, i.e. particle sizes > 2.5 μm, that also may
influence the perception of the IAQ, cf. Bottcher (2001). The particle
surface-active properties may also influence the nature of perception of
IAQ, if the mucus membranes are susceptible, i.e. desiccated or dena-
turized; for instance, one may speculate whether reporting of “dry air”
reflects “slightly irritating”air that is triggered by odor, while desic-
cated mucus membranes or eyes may interact more readily with active
particle surfaces or sensory irritants.
3.1.3. Particles
Particles impact the IAQ and health by their chemical and physical
properties, but they may also be carriers of influenza virus. Particle
concentration, chemical composition, particle size (diameter) and
shape, particle deposition and resuspension, and hygroscopic growth
appear to depend on RH, however, the picture is far from complete; the
mechanisms behind resuspension are by nature complex that depend on
many factors and their interaction (Qian et al., 2014). For instance,
larger particles, in general, show larger resuspension by walking at low
RH in laboratory settings (Kivistö and Hakulinen, 1981;Qian et al.,
2014) and low deposition of particles < 1 μm(Han et al., 2011). This
agrees with a 6.4 μg/m
3
decrease of PM
2.5
per 10% increase of RH in
schools during winter; however, an opposite trend was observed during
summer time (Fromme et al., 2007). Increase of RH 3–10% from very
low RH in long-haul flights significantly lowered the concentration of
respirable particles from 6 to 1 μg/m
3
; similar observation was seen for
mold and bacteria (Lindgren et al., 2007). Modeling indicates that
shorter people may be exposed to higher concentrations of resuspended
particles and pathogens, than taller people, but experimental con-
firmation is needed (Khare and Marr, 2015).
The resuspension of particles depends on walking style and density;
further, particle-substrate interaction and substrate interactions like the
microscopic surface roughness (Qian et al., 2014;Qian and Ferro, 2008;
Tian et al., 2014). For example, Tian et al. (2014) observed that course
particles (3–10 μm) resuspend with a 2–4 higher concentration from car-
pets in comparison with hard floorings, while no difference was observed
for fine particles; however, elevated humidity caused enhanced re-
suspension on high-density carpets, while hard surfaces showed the op-
posite effect. Furthermore, the water solubility of the particles is im-
portant, thus, resuspension was higher for hydrophobic (e.g. cat and dog
fur) respirable particles than hydrophilic ones (e.g. dust mites) (Salimifard
et al., 2017). This is in some contrast to observations reported about
human emissions of course particles from frictional interaction between
humanskinandclothing.Forinstance,Bhangar et al. (2016) reported an
increase of emissions of fluorescent particles from human subjects at ele-
vated RH in a climate chamber; however, differentiation between re-
suspension from the floor and body envelope emissions was not possible.
This is further complicated by use of skin moisturizer, where mean
emission rates of fluorescent particles differed insignificantly at low and
high RH, but lower humidity was associated with smaller emission peak
amplitudes of the fluorescent particles (Zhou et al., 2016).
Overall, laboratory experiments indicate more resuspension of large
particles and less for smaller particles at low RH, however, surface
dependent. More experience from field studies is warranted to under-
stand the mechanisms and chemical nature of the particles that influ-
ence the resuspension by indoor air humidity.
3.1.4. Work performance
The “indoor productivity index”in “normal”and well-ventilated
offices in buildings, characterized as “not sick”, has been assessed by a
questionnaire study of 484 office workers and 21 green house em-
ployees (Wiik, 2011). The self-assessed productivity depended equally
on psychosocial and environmental factors, and RH was identified as
important. This agrees with the observation of a few percent reduced
visual data acquisition for certain office tasks among young students
that were exposed to low RH for 4 h (Wyon et al., 2006); an effect that is
expected to become more pronounced among elderly office workers, cf.
Wolkoff(2017).
Overall, the immediately perceived IAQ appears more acceptable at
low RH and low temperature, which reflects altered VOC emission
profiles from material surfaces or altered surface reactions with oxi-
dants. The common reported “stuffy or dry air”may thus be affected
not only by alteration in the VOC emission profile, but also at the same
time by alteration of the dynamics, composition, deposition and re-
suspension of inhaled particles; possibly in concert with susceptible
eyes or mucus membranes in the upper airways at low RH. This con-
trasts the outcome of many intervention studies which show the ben-
eficial effects by increase of the indoor air humidity from low RH as
shown in Table 1.
3.2. Sensory irritation in eyes and upper airways and odor
3.2.1. Rodents exposed to sensory irritants at different relative humidity
levels
The only standardized and validated animal bioassay, which pre-
dicts sensory irritation in the airways in humans from airborne che-
micals, is the Alarie test (Nielsen and Wolkoff, 2017). It is a mice
bioassay, which uses the trigeminal reflex-induced decrease in the re-
spiratory rate, where the 50% decrease (RD
50
) has been correlated with
occupational exposure limits (threshold limit values) caused by sensory
irritation in the upper airways; furthermore, no-observed-adverse-ef-
fect-levels may be predicted according to Kuwabara et al. (2007). Since
sensory irritation in the eye and upper airways is mediated by the same
nerve system (Trigeminus), the predicted limit is similar for both tar-
gets, although eyes may generally show a slightly lower limit as shown
in human exposure studies (Doty et al., 2004).
Data from animal inhalation studies about sensory irritation in the
upper airways are summarized in Table 2. The studies indicate that
sensory irritation in the upper airways is unaffected by low RH; how-
ever, o-albumin-sensitized mice appeared to be less affected than
normal mice regarding bronchoconstriction at very high formaldehyde
levels (Larsen et al., 2013). This observation is compatible with slightly
less sensory irritation in nose and throat in asthmatic subjects in com-
parison to healthy subjects, when exposed to a steady-state reaction
mixture of ozone (max 37 ppb) and limonene (36 ppb) [resulting
in < 10 ppb formaldehyde (Atkinson and Arey, 2003)] for 3 h in a
controlled and blinded chamber study (Fadeyi et al., 2015). It has been
proposed that the excess mucus in the airways of asthmatics and in the
sensitized animals has a scrubbing (protective) effect, thus explaining
the difference between the healthy and asthmatic subjects and similarly
in normal and sensitized mice exposed to formaldehyde or a reaction
mixture of ozone and limonene (Hansen et al., 2016;Larsen et al.,
2013).
No major influence on sensory irritation was observed in mice ex-
posed to ammonia at dry versus humid conditions; however, a minor
effect was seen in rats (Li and Pauluhn, 2010). This effect should be
considered cautiously due to the breathing parameter, RD
50
used for
comparison, which reflects the combined effect of sensory irritation and
time of inspiration, while “time of break”(not reported) before
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
379
initiation of exhalation is a more specific measure of sensory irritation,
cf. (Wolkoffet al., 2012). The animal data agree with statistically un-
altered lateralization thresholds for sensory irritation at humid and dry
conditions among eight volunteers (Monsé et al., 2016).
Many rodent studies have shown adverse effects on the eye physiology
by exposure to low RH, see Table 2. Thus, less tear production and dry spot
formation in the (precorneal) eye tear film has been observed (Barabino
et al., 2005;Chen et al., 2008)andepithelialdamage(Xiao et al., 2015).
All in all, the studies show that low RH aggravates the stability of the eye
tear film, which becomes more susceptible and consequently initiates a
cascade of adverse inflammatory reactions (Wolkoff,2017). For instance, a
destabilized eye tear film relative to a stable one may be more susceptible
to inflammatory reactions by exposure to titanium dioxide nanoparticles
as shown in a rat model (Han et al., 2017).
3.2.2. Sensory irritation and odor in humans
Induction of sensory irritation in the upper airways (nose) by strong
sensory irritants (chemicals) appears independent of the RH in animal
studies, see above. This is contrary for odor thresholds in humans. For
instance, a lower threshold was found for butanol than at dry conditions
(80% vs 30% RH), at least in comparison at hypobaric conditions
(Kuehn et al., 2008), while no effect on RH was found for pyridine
(Callado and Varela, 2008), which in part agrees with clinical experi-
ence (Philpott et al., 2007). The studies, however, are not directly
comparable and the contradictory data does not allow for a general-
ization.
One study at three different geographical locations and humidity
indicated a trend of “a higher overall skin irritation level at dryer cli-
matic conditions for both positive (0.1% sodium lauryl sulfate) and
negative controls (0.9% saline) (Trimble et al., 2007). Asthmatics may
be less sensitive to inhalation of strong water-soluble irritants, like
formaldehyde, than non-asthmatics. However, individuals with allergic
diseases (e.g. allergic rhinitis) may perceive IAQ and ‘dry air’differently
than normal subjects and possibly react differently to other pollutants,
e.g. unpleasant odors. Thus, more secure and standardized information
is warranted about the influence of humidity on odor thresholds.
Table 2
Animal studies: airway (sensory irritation) and ocular surface effects.
Study Method Rel. hum.
%
Observation
Barabino et al.
(2005)
Normal mice (5 for each condition) exposed to dry air in controlled
environmental chamber and compared with control mice (n =30) at
room temperature. Ocular surface examined after 3, 7, 14 and 28 days
of exposure.
18.5
50–80
Low RH caused a decrease of tear production and increase of
fluorescein corneal staining in normal mice compared to control mice
exposed at 50–80% RH. A significant drop ingoblet cells after 7 days
was observed in mice exposed to low RH.
Chen et al. (2008) Mice (5 for each condition)) were exposed to controlled dry
environment. The ocular surface was examined after 3, 7, 14, 28, and
42 days of exposure at room temperature.
15 Aqueous tear production decreased, while an increase was observed for
corneal fluorescein staining, thinning, and accelerated desquamation of
the apical corneal epithelium.
Upregulated apoptosis was observed on the ocular surface.
Larsen et al.
(2013)
Mice (5 for each condition) were exposed to formaldehyde
(4–5.7 ppm) for 1 h.
Respiratory parameter, time of break, was measured.
Sensitization of mice did not cause increased sensitivity to sensory
irritation of formaldehyde at dry conditions.
Non-sensitized mice < 5 At humid conditions, sensitized mice were more sensitive to pulmonary
effects at high formaldehyde concentrations, while under dry
conditions the non-sensitized animals were more sensitive.
Non-sensitized mice 85
Sensitized (ovalbumin) mice < 5
Sensitized (ovalbumin) mice. 85
Han et al. (2017) Normal and evaporative dry eye induced rats (6 in each condition)
were exposed for 24h to titanium dioxide particles (< 75 nm;
0.5 mg/ml) by installation and compared with sham condition;
corneal clarity and tear samples were measured.
30 Evaporative dry eye induced rats were more susceptible (e.g.
inflammatory cell infiltration on the ocular surface) to titanium dioxide
particles than normal rats.
50
Li and Pauluhn
(2010)
Mice and rat (male) bioassay. Animals (4 per condition) were exposed
to ammonia and respiratory rate RD
50
was measured.
Reduction of RD
50
(%)
0 582ppm, mice
95 732 ppm, mice
*
0 972ppm, rat
95 905 ppm, rat
Lin et al. (2009) Guinea pigs (7–9 for each condition) exposed to hot (40.5 °C)
humidified air for 4 min via a tracheal tube to the lung and compared
with control group exposed to humidified room air. Pulmonary
resistance was measured.
Not
known
(Expiratory airway temperature is significantly higher in asthmatics,
2.7 °C).
Elevated tracheal temperature from 36.4 to 40.5 °C induced immediate
transient airway constriction mainly mediated through cholinergic
reflex, probably elicited by the activation of the TRPV1 temperature-
sensitive receptor −water is believed to be a critical factor in delivery
of the heat load. Further, increase of total pulmonary resistance. In
contrast, hyperventilation with humidified air at room temperature did
not alter pulmonary resistance.
Nakamura et al.
(2010)
Female rats were exposed in a swing to dry air for 6 h daily period.
Lacrimal function and morphology were evaluated after undergoing
10 days of the swing procedure.
25 It was shown that not only excess evaporation of tear fluid but also
hypofunction of the lacrimal gland contributes to the pathogenesis of
visual display unit-associated dry eye in humans.
Suhalim et al.
(2014)
Mice (n = 10) exposed to a controlled drafty dry air environment.
After 5 and 10 days eye samples were analyzed.
30–35 Dry air environment has a direct effect on the Meibomian gland function
−a 3-fold increase in basal acinar cell proliferation after 5–10days and
abnormal meibocyte differentiation and altered lipid production.
Wilkins et al.
(2003)
Mice (4 at each condition). Respiratory rate (RD
50
) reduction by
exposure to ozone/limonene mixture (16 s old) and ozone/isoprene
mixture (90 s old) at different RH.
Reduction of RD
50
(%)
0 By ozone/limonene: 33
32 22
*
0 By ozone/isoprene: 56
32 42
*
Xiao et al. (2015) Mice (60 for each condition) were exposed for 1, 2, 4, and 6 weeks to
controlled dry environment at room temperature, and air velocity
2.2 m/s. Further, mice were housed in normal laboratory conditions.
The ocular surface was analyzed.
13 vs 60 Dry environment induced corneal epithelium damage (apoptosis) and
stimulated inflammatory cytokine production in conjunctiva and
lacrimal gland. Further, lacrimal gland structural alterations were
observed.
RD
50
= concentration that causes 50% reduction of the respiratory rate.
* Statistically significant.
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
380
3.2.3. Ophthalmological investigations of the precorneal tear film and
ocular comfort in humans
An intact and stable eye tear film is essential for visual acuity and
ocular comfort, in general. The prevalence of external eye symptoms
continues to be high in European and Japanese offices (Bluyssen et al.,
2016;Yokoi et al., 2015). Retrospectively, the prevalence has not de-
clined substantially during the last decades, despite lower emitting
building materials and modern buildings (Bluyssen et al., 2016;
Wolkoff, 2013).
Many ophthalmologic studies have demonstrated how fast low RH
aggravates the stability of the eye tear film, i.e. break-up or thinning of
the eye tear film resulting in less tear production or exacerbation of
water loss, see Table 3. This leads to desiccation and hyperosmolarity in
the eye tear film and initiation of a cascade of inflammatory reactions
Table 3
Human exposure and field studies at different humidity conditions −ocular surface.
Study Approach Rel. hum.% Observation
Abelson et al.
(2012)
Dry eye patients (n = 33) exposed for 1½ h Low Decrease of mean break-up area induced by low RH; correlation with
other measures of dry eye diseases and demonstration of
compensatory mechanisms in dry eye patients.
Abusharna and
Pearce (2013)
Healthy subjects (10 men, 2 women) were exposed for
1 h followed by tear and ocular measurements
40 vs 5 Evaporation rate of water, lipid layer thickness, ocular comfort, low RH
significantly adversely affected precorneal film stability and production.
Tear film parameters became like dry eye patients after 1 h at low RH.
Alex et al. (2013) Normal subjects (n = 15) and dry eye patients (n = 10)
were exposed for 1½ h.
15–25 Significant increase of corneal and conjunctival dye staining (dry spot
formation) in both groups, but greater staining in superior cornea in
dry eye patients. Eye blink frequency between 30 and 90 min was
higher in dry eye patients.
Gonzales-García
et al. (2007)
Contact lens-wearers (n = 10) with minimum of
symptoms were exposed for 2 hours without contact
lens and with contact lens at 2 RHs. Dry eye signs were
evaluated before and after each exposure
19 (22 °C)
35 (24 °C)
Without contact lens: Significant changes were observed in comfort,
noninvasive BUT, conjunctival hyperemia, and phenol thread test at
low RH as opposed to normal conditions (no changes).
With contact lens: Same changes were observed in both conditions.
These returned to normal after about 1 month, i.e. reversible.
Galor et al. (2014) United States veteran study. All patients seen in a
veteran administration eye clinic between 2005 and
2011; retrospective analysis
National Climatic
Data Center and
NASA adm
The most important risk factors of dry eye symptoms were shown to
depend primarily on air pollution (optical measurement of aerosols)
and pressure (high altitude). Furthermore, higher RH and wind speed
was inversely associated with the risk of dry eye symptoms.
Hirayama et al.
(2013)
Dry eye patients (n = 10) were exposed during
minimum 4 h daily visual display unit (VDU) work to
Moist Cooling Air Device (MCAD; 100–300 μm
droplets) for 5 working days; similarly, patients
(n = 10) carried VDU work without MCAD
+/−MCAD in
offices
MCAD significantly improved functional visual acuity, lowered BUT
and symptom score (less dryness). Strip meniscometry and
evaporation rate of water significantly improved. No significant
changes in lipid layer stability or corneal staining between the 2
groups. Blink frequency was significantly increased without MCAD.
Lan et al. (2011) Subjects (n = 12; male/female = 1:1) doing office
work at 23 °C and 30 °C
21–22 Ferning test showed an increase of type III and IV patterns that
indicate substantial alteration of the precorneal tear film
“composition”, i.e. lower tear film quality, at the high temperature.
López-Miguel et al.
(2014)
Mild to moderate dry eye patients (n = 19) and
asymptotic controls (n = 20) were exposed in climate
chamber for 2 hours. Single-item score dry eye
questionnaire and diagnostic tests were performed
before and after the exposure period
5 Significant increase in corneal staining and significant decrease in
fluorescein break-up time were observed in patients and controls.
Also, a significant increase in matrix metallopeptidase.
In controls: significant decrease of epidermal growth factor and
significant increase of interleukin-6 levels were observed after
exposure.
Melikov et al.
(2013)
Subjects (n = 30) were exposed for 4 h by personalized
ventilation (PV) or without at different temperatures
and 15 min video recording and analysis of eye blink
frequency and Ferning test of tear liquid
+PV 70–26 °C, 28 °C
-PV 40–23 °C
Increase of T and RH without PV reduced blink frequency. Only
significanceat26°C/70%RH,notat28°C.UseofPV,i.e.23°C/40%RH
decreased blink frequency significantly in comparison with 26 °C/70%
RH, indicating that temperature perhaps is more important than RH.
Ferning test showed a decreasing trend in precorneal film quality, by
disappearance in Grade I quality going from neutral condition to
higher temperature and RH. Use of PV slightly improved the quality of
the precorneal tear film. Data, however, should be interpreted with
caution. Ferning test should be compared at comparable conditions,
thus interpretation of data is difficult.
Madden et al.
(2013)
Dry eye patients (n = 3) and normal subjects (n = 3)
were exposed in controlled climate chamber. Tear
evaporation rate was measured after 0, 5, 10, 15, 20 and
25 min. No ninvasive BUT and tear evaporation rate w ere
determined at 5% to 70% R H in dry ey e patients (n = 10)
and normal subjects (n = 10); T = 72 °F (22.2 °C)
40 Ten min required for reaching steady-state of the tear evaporation rate
(peak after 5 min) and no chance in noninvasive BUT. Dry eye patients
had higher evaporation rate and shorter noninvasive BUT than normal
subjects at 5% and 40% RH, but not at 70%. Emulsion drops helped.
Nakamura et al.
(2010)
Cross-sectional survey of tear film characteristics in
1025 office workers during VDU work.
VDU users have less tear secretion (impaired lacrimal function), less
the more VDU use, both on a yearly duration and daily basis. Dry
conditions cause less tear secretion.
“Human and rat studies provided the evidence that not only excess
evaporation of tear fluid but also hypofunction of the lacrimal gland
contributes to the pathogenesis of VDU-associated dry eye.”
The study suggests that a proper number of eye blinks is required for
healthy lacrimal gland function to occur. Since VDU use suppresses
the blink frequency, modifications, such as the use of bigger and
clearer characters, should be considered when trying to increase the
blink frequency, in addition to modifying daily working conditions or
lifestyles.
Norbäck et al.
(2006)
Aircraft cabin crew (n = 70–79) were exposed to low or
elevated (blind) humidity for 8 hours transatlantic flight.
10–14
21–25
Significant improvement of precorneal tear film stability (i.e. longer
subjective BUT) and decrease of perceived eye dryness and fatigue.
(continued on next page)
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
381
(Wolkoff, 2017). For example, one-hour low RH exposure to healthy
subjects resulted in tear film parameters like in dry eye patients
(Abusharna and Pearce, 2013).
The instability of the eye tear film may increase the formation of
(local) dry spots, which enhances direct exposure of the corneal epi-
thelium to pollutants; thus, the eyes may possibly become more sus-
ceptible and react faster to external stimuli like sensory irritants (e.g.
formaldehyde) and other aggressive pollutants, e.g. oxidants like ozone
and particulate matter (Wolkoff, 2017).
Attempts have been carried out to reduce dry symptoms among
office workers by various techniques that locally elevate the humidity.
For example, even a modest increase from 45% to 50% RH for one hour
showed a significant increase of the eye tear film stability by increase of
the non-invasive break-up time followed with a significant dry eye re-
lief (Wang et al., 2017). Similar positive effects have been shown for the
use of glasses with moist inserts, e.g. Korb and Blackie (2013);Ogawa
et al. (2017);Waduthantri et al. (2015).
Overall, the human eye tear film is susceptible to low RH, which ag-
gravates its stability, and likely the susceptibility to aggressive chemicals
and particles, and which potentially may initiate a cascade of reactions
like hyperosmolarity leading to inflammatory reactions; however, even
modest local increase of RH may be beneficial by dry eye relief. Further
studies are necessary to explore the interplay between low humidity, tear
film stability and exposure to aggressive indoor air pollutants.
3.3. Human climate chamber studies –airway effects and sleep quality
3.3.1. Airway effects
The major function of the nose and nasal cavity is to humidify and
warm inhaled air; thus, the anterior part of the nasal cavity contributes
within a short nasal passage to air conditioning of inspired air (Keck
et al., 2000). The temperature of the nasal cavity strongly depends on
feet temperature; for instance, the conditioning capacity in response to
cold-dry-air is significantly higher at 40 °C feet temperature than 30 °C,
i.e. the ability of the nose to condition inspired air without concomitant
change of volume of the nasal cavity (Naclerio et al., 2007).
Mucous membranes lose water by evaporation and heat in the hu-
midification and warming processes (Cruz and Togias, 2008;Naclerio
et al., 2007). Thus, the mucosal function depends strongly on the hu-
midity and heat in the inhaled air, the exposure time, and the health of
the individual (Williams et al., 1996). Hundred percent RH at core
temperature is moisture neutral, “and preserving maximum mucociliary
transport velocity”(Williams et al., 1996); either lower or higher RH
will alter the mucous viscosity and the mucociliary activity.
The respiratory epithelium plays an important role by evaporation
of water from its surface (desiccation). This continuous need for eva-
poration may lead to a hyperosmolar environment on the surface of the
epithelium. Increased ventilation may result in a larger hyperosmolaric
surface that moves more distal, and this may stimulate the epithelial
cells releasing inflammatory mediators. Cold-dry-air led to significantly
higher osmolarity than methacolin or histamine, thus confirming that
the osmolarity in nasal secretions has increased after cold-dry-air
challenge (288 to 306 mOsm/kg H
2
O) (Naclerio et al., 2007). “De-
siccation (dehydration) of the epithelium includes desquamation, leu-
kocyte infiltration, vascular leakage, and mast cell degranulation, all of
which may worsen inflammation”. Thus, the epithelial cells may be
stimulated to release inflammatory mediators if the hyperosmolaric
surface is not restored (Naclerio et al., 2007). Further, hyperosmolar
challenge may cause histamine and leukotriene (C4) release. It is con-
cluded that the histamine release is probably caused by hyperosmolar
Table 3 (continued)
Study Approach Rel. hum.% Observation
Paschides et al.
(1998)
Three geographically and climatically different groups
(n = 55–57, each) were tested for eye tear film
stability.
•Dry, warm and
heavy pollution
•Dry, warm, and
low pollution
area
•Cool, humid and
low pollution
The precorneal tear film stability (Schirmer-1 test and BUT) was
influenced by low RH and high temperature. The outdoor pollution
(traffic) may have impacted the tear film quality differently.
Sunwoo et al.
(2006a)
Healthy students (n = 16) were exposed to different
RH for 90 min.
10, 30, 50 Significant increase in eye blink frequency below 30% RH.
Takahashi et al.
(2010)
Eye steaming after VDU work at different humidity. Increase of RH at the periocular region improved subjective amplitude
of accommodation and near vision.
Tesón et al. (2013) Dry eye patients (n =20; 6 males) and dry eye control
patients (n = 15: 5 males; 45% RH) were exposed in
simulated in-flight condition for 2 hours at 23 °C.
5
45
Tear IL-6 and matrix metalloproteinase increased significantly, while
epidermal growth factor decreased significantly. Dry eye patients
suffered significantly by lower BUT, tear volume, and an increase of
corneal staining. A mild increase of corneal staining was seen in the
control patients.
Uchiyama et al.
(2007)
Dry eye patients (n = 18) and healthy subjects
(n = 11) were exposed to different RH.
20–25
40–45
Evaporation rate increased 100% from normal to low RH in both dry
eye patients and healthy subjects.
Um et al. (2014) Korean adults (n = 16431; age > 30) were analyzed
for the spatial epidemiological pattern of dry eye
disease prevalence.
Lower RH, sunshine exposure, and degree of urbanization (air
pollution) were suggested to be associated with increase of dry eye
disease.
Walsh et al. (2012) Cross-sectional design assessment of patients (n =111;
56 males; age = 77 ± 8) admitted to acute unit. Dry
eye questionnaire, dryness (VAS), noninvasive BUT,
hydration, and tear osmolarity.
Dry eye patients showed higher plasma osmolarity, thus indication of
suboptimal hydration in comparison to non-dry eye patients. Whole-
body hydration appears to be important.
Wang et al. (2017) The RH was randomly elevated by use of a desktop
USB-powered humidifier in a masked crossover study
with VDU users (n = 44) for 1 hour. The eye tear film
quality was measured, and the eye comfort was
assessed by the users.
45–50 BUT increased from 6.4 to 9.0 sec at 50% RH. The lipid layer thickness
and tear meniscus were unaltered. The users (36%) of humidifier
reported a significant improvement in eye comfort versus 5% without
humidifier at 50% RH. 7% of the users reported less comfort at 50%
RH and 48% reported less comfort at 45% RH.
Wyon et al. (2006) Young subjects (n = 30; 13 males) were exposed for
5 hours to different RH.
5, 15, 25, 35 Increased eye blink frequency and eye discomfort and reduced visual
data acquisition at low RH.
BUT = break-up time. MCAD = moisture cooling air device. NBUT= noninvasive break-up time. PV = personal ventilation. RH = relative humidity. T = temperature. VDU = visual
display unit.
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
382
stimuli in mast cells and the release is greater among those responding
to cold-dry-air (e.g. asthmatics) than non-responders. Furthermore, in
the end, dryness of the epithelium may increase bacterial adherence
and allows for greater penetration of foreign species, like particles
(Naclerio et al., 2007).
Table 4 shows studies about the impact on lung function in normal
and asthmatic subjects exposed to different humidity. For example,
asthmatic patients appear to be more sensitive to cold dry air than
normal subjects (Hanes et al., 2006;Naclerio et al., 2007). However, for
thermally induced asthmatics the issue of airway desiccation, i.e. hy-
perosmolarity, per se, does not appear to be important; further, there is
indication that the “cooling-rewarming gradient, rather than desicca-
tion is important”(McFadden Jr. et al., 1999). The observation that
humidity is of less importance among asthmatics is compatible with the
studies by Larsen et al. (2013) and Fadeyi et al. (2015). These studies
showed that ovalbumin-sensitized mice (“asthmatic”) and asthmatics
were less affected than non-sensitized mice or normal subjects, re-
spectively, from exposure of formaldehyde or an ozone-limonene in-
itiated reaction mixture.
Nasal mucociliary transport (an epithelial function) is an important
factor in exchange of heat and water, and protection of the mucosal
interface; this requires an periciliary fluid layer of a certain height
(thickness) for an efficient mucociliary transport (Naclerio et al., 2007).
Thus, the saccharin mucociliary clearance time in the upper airways
was significantly lower in elderly subjects at low RH in comparison with
younger subjects, which appear to be less sensitive (Sunwoo et al.,
2006a, 2006b). This could be interpreted that the upper airways of
elderly are less efficient in achieving moisture neutrality and maximum
mucociliary transport. However, young subjects also showed longer
clearance time below 30% RH, experienced sensation of dry eyes at
entering the exposure chamber, while the sensation of dry nose and
throat became significant after 90 min (Sunwoo et al., 2006a). Sub-
jectively, the elderly group had difficulty in feeling dryness in the upper
airways (nose), despite longer clearance time, but the young subjects
did feel dryness after 180 min. In general, subjects felt greater dryness
in the throat. This agrees with a previous study that showed a sig-
nificant increase in clearance time from 11.9 min at 40–43% RH
breathing air for 30 min to 18.5 min at 0.1% RH among healthy subjects
(Salah et al., 1988). Sunwoo et al. (2006a, 2006b) recommended
RH > 30% to avoid dry eyes and RH> 10% to avoid nasal dryness. At
the same time, nasal patency is lower at dry and/or cold air in com-
parison to room air (Zhao et al., 2011); furthermore, the forced ex-
piratory volume within 1 s (FEV
1
) was shown to reduce by increase of
water loss from extended dry air exposure (McFadden Jr. et al., 1999).
Overall, except for longer saccharine mucociliary clearance time
among elderlies, asthmatics appear to be more susceptible to cold dry
air and at the same time more robust to exposure to strong (water-
soluble) sensory irritants than non-asthmatics at low RH. While it is
well established that RH less than 30% aggravates the eye tear film
leading to eye symptoms like “dry eyes”, the sensation of dry nose and
throat also occurs in the nose and throat after some latency and without
pollution, but more pronounced at RHs below 10%. Further studies are
necessary to clarify the interplay between clearance time, humidity,
and indoor pollution, e.g. particles.
3.3.2. Continuous positive airway pressure in patients
Table 5 shows studies with patients suffering from obstructive sleep
apnea. Humidified (heated) air appears to reduce nasal symptoms in the
patients, but not quality of life and sleepiness (Ryan et al., 2009;Nilius
et al., 2008, 2016), but methodological issues may obscure the result,
e.g. sleepiness and quality of life, according to Ruhle et al. (2011) and
Ugurlu and Esquinas (2016).
Benefits of an increase of RH in bedrooms is controversial in view of
the consensus that elevated humidity (water activity) in moisture-da-
maged building constructions is associated with adverse health effects,
e.g. by increase of the exposure risk to fungi, mildew, dust mites, etc.
(World Health Organization, 2009); however, increase of bedroom RH
has been proposed to have a beneficial effect (Myatt et al., 2010).
Overall, based on the studies, humidified breathing air appears to be
beneficial for high-risk patients with nasopharyngeal complaints (Ryan
et al., 2009;Nilius et al., 2008, 2016). However, effects on sleepiness
and quality of life are unclear and need further documentation. More
controlled field studies are necessary to identify the effects of tem-
perature and humidity in bedrooms and associated ventilation for fur-
ther substantiation.
3.4. Influenza virus survival and transmission
Table 6 shows influenza virus survival and transmission studies at
different air humidity. Cold temperature and low RH has been asso-
ciated with increased occurrence of respiratory tract infections, in line
with increased survival and transmission efficiency of influenza virus,
e.g. from coughing. Thus, RH > 40% greatly reduces the infectivity of
virus, e.g. Lowen et al. (2007);Mäkinen et al. (2009);Noti et al. (2013);
Myatt et al. (2010). For instance, Myatt et al. (2010) estimated that an
increase of RH to 47% reduced the influenza survival by 17–32% with
an operating humidifier in a bedroom. Furthermore, it has been mod-
eled that low temperature and low AH prevents disruption of the in-
fluenza virus as opposed to higher temperature and humidity (Koep
et al., 2013;Ud-Dean, 2010).
Several studies indicate favorable survival conditions for some in-
fluenza viruses at cold and low RH (see Table 6). Experimental in-
adequacy of the studies should be considered carefully together with
the overall complexity of transmission and survival, and associated
mechanisms of infection (Memarzadeh, 2012;Yang and Marr, 2012). At
least three mechanisms have been proposed, cf. Memarzadeh (2012);
RH interacts with the host’s airways, i.e. desiccation of mucus mem-
branes in nose and upper airways may cause epithelial damage and
reduced mucociliary clearance (an important defense mechanism), thus
the airways may become more susceptible to viral infection. Second,
RH impacts the virus-aerosol stability that depends on the physical-
chemical properties; thus, virus with a lipid envelope are more stable in
dry air as opposed to a non-lipid virus envelope (Morawska, 2006). For
instance, high RH decreases the survival of lipid-enveloped virus, like
influenza A and influenza b (Schaffer et al., 1976;Tang, 2009;Teller,
2009). Third, RH impacts virus/droplet dynamics, i.e. size, surface
properties, water content, and consequently transmission and deposi-
tion, etc. Probably, all three mechanisms act in a concerted manner.
Perhaps, more important is the strong association identified between
AH and influenza survival and transmission as reviewed by (Lipsitch
and Viboud, 2009). Finally, it has been hypothesized that disease
transmissions could depend on resuspension of floor dust, thus shorter
people may be exposed to higher levels of infectious particles than taller
ones (Khare and Marr, 2015); for resuspension of particles, see the
subsection “Particles”.
Overall, many studies have shown that survival and transmission
potential of influenza viruses are inversely associated with AH rather
than RH in wintertime, e.g. Lipsitch and Viboud (2009);Metz and Finn
(2015);Shaman and Kohn (2009);Shaman et al. (2010). This, in part,
agrees with a large cross-over study among military conscripts
(Jaakkola et al., 2014). Thus, indicating that cold and low RH condi-
tions favor survival and transmission for some influenza virus, which
also include viruses like RS virus, human rhinovirus, and avian influ-
enza virus, e.g. Ikäheimo et al. (2016) and Davis et al. (2016b). How-
ever, the opposite has been observed for other virus types (Morawska,
2006;Weber and Stilianakis, 2008). Thus, the mechanisms of survival
and transmissions are far from fully understood and generalization
about viral transmission and survival, due to the complexity, is not
applicable, but should be dealt with virus-by-virus, cf. (Morawska,
2006;Weber and Stilianakis, 2008). Clearly, ventilation rates of fresh
and adequately humidified air and temperature play an important role
that needs more research attention for substantiation about the
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
383
Table 4
Human exposure studies at different relative humidity conditions –the airways.
Study Approach Number of
subjects
Age
years
Observation
Baroody et al. (2008) Double-blind, placebo- controller, cross-over, clinical trial of patients. 20 Nasal allergen challenge probably initiates nasal and a nasal ocularreflex.
Cruz and Togias (2008) Review paper about upper airway reactions to cold dry air in context of cold-air
rhinitis.
It is proposed from that cooling and water loss/hyperosmolarity are key candidates for a
clinical response. However, it is argued that water loss/hypertonicity is more important, but
the two stimuli work in concert. Hyperosmolarity stimulates the sensory nerves that generate
a central reflex (contra-lateral secretory response), but can also release inflammatory
biomarkers (neuropeptides) by the same nerves.
Freed and Davis (1999)
animal
Canine exercise-induced model to investigate hyperventilation at warm humidified
air vs dry air.
Dry air challenge increased peripheral airway resistance, the airway surface volume, and the
surface osmolarity. Data support that changes in airway osmolarity during hyperventilation
initiate peripheral airway constriction.
Hanes et al. (2006) Comparison of the response of subjects with allergic rhinitis (AR) and asthma (ARA)
and subjects with only AR to cold dry air.
24 (ARA) vs 17
(AR)
Patients with ARA were more responsive to cold dry air than subjects with AR alone.
Hashiguchi et al.
(2013)
Young healthy male subjects were exposed for 6 h to 10% and 60% RH and pressure
(sea level and 2000 m altitude (=low pressure), independently.
14 23 Body fluid loss was significant at low pressure, but combined low pressure and low RH
increased the loss even further. Blood viscosity increased also, but low RH alone did not alter
the blood viscosity significantly; this, however, cannot be excluded as a possibility, i.e. more
subjects required.
Kalhoff(2003) Review paper about patients with asthma and chronic bronchitis and dehydration. Still unclear about mild dehydration as risk factor of broncho-pulmonary disorders.
Khosravi et al. (2014) Allergic rhinitis (AR) patients and healthy subjects (HS) were exposed for 4 min to
hot (49 °C; 75–80% RH) humid air and room air (21 °C; 65–75% RH), respectively,
during hyperventilation.
7 (AR)
6 (HS)
49
21
Coughs/min in AR patients increased from 0.1 before challenge to 2.4 during and 1.8 first
8 min after end of challenge, for hot air exposed, only. The hot air challenge also caused
respiratory discomfort (throat irritation) among AR patients. No effects seen among healthy
subjects. Bronchoconstriction was not seen in both groups. Upper airways seem to be
triggered by hot air.
Kim et al. (2007) Prospective trial of 2 groups of adult patients under general anesthesia: controls did
not receive warm and humidified air (27 °C; 76% RH), while another group received
warm and humidified air (36 °C; 99.5% RH).
200 No appreciable differences in complaints after active warming and humidification of inspired
gases (air) after 2 h.
Kuehn et al. (2008) Male volunteers exposed to 30% or 80% RH and butanol. 27 22 ± 6 High RH showed lower odor threshold for butanol, i.e. enhanced sensitivity.
Lindemann et al.
(2003)
Nasal airway resistance was measured in healthy subjects by active anterior
rhinomanometry and compared with intranasal RH at different locations.
15 30 (25–42) Degree of water saturation did not correlate with active anterior rhinomanometry, i.e. no
correlation between nasal resistance and water vapor saturation at different anterior nasal
segments during the nasal daily cycle.
McFadden Jr. et al.
(1999)
Thermally induced asthma was investigated by mucosal dehydration in subjects
carrying out isocapnic hyperventilation of dry air at constant level for max 8 min.
Lung functions (FEV
1
) were investigated at cold (−12.5 °C) and ambient (24.3 °C) T.
Water loss in intrathoracic airways was calculated.
828±2
•Less water loss at cold temperature and FEV
1
decreases as water loss increases.
•The effect of water loss increases with time.
•%ΔFEV
1cold8min
= 30%, water loss = 4.7 mg
•%ΔFEV
1warm8min
= 16%, water loss = 7.1 mg
The issue of airway dehydration, i.e. hyperosmolarity, per se, does not appear to be of major
importance for thermally induced asthma. “When respiratory heat exchange increases in
asthmatics the intensity of obstruction follows suit”;a“cooling-rewarming gradient, rather
than airway desiccation”.
Melikov et al. (2013) Students (n = 30) were exposed to high temperature (26 or 28 °C; 70% RH) for 4 h
and compared with baseline (23 °C, 40% RH) and with additional PV (personal
ventilation: 24 °C, 40% RH).
15 male
15 female
The exposure to high T and RH results in lower acceptability of the thermal climate. The
subjects’controlled use of a PV improved the thermal sensation and acceptance of climate.
Performance appeared to decrease at high temperature and RH. Use of PV improved, i.e. the
ability to work was higher during PV conditions.
Salah et al. (1988) Saccharin mucociliary clearance time and nasal breathing were measured after
30 min exposure of non-smoking subjects (n = 11) to dry air (0.1% RH) or room air
(40–43% RH).
6 males
5 females
17–38 Saccharin mucociliary clearance time was significantly longer at breathing dry air (18.5 min)
versus room air (11.9 min).
Sunwoo et al. (2006b) Saccharin mucociliary clearance time, hydration state of skin, transdermal water
loss were measured in non-smoking elderly and students. Rating of thermal, dryness
and comfort.
8 students
8 elders
22 ± 1
71 ± 4
Saccharin mucociliary clearance time was significantly longer in the elderly group at 10% RH
after 90 and 180 min of exposure. No change in saccharin mucociliary clearance time in the
students at the different RH.
Experimental conditions:
Precondition: 25 °C/50% RH (50 min); exposure for 180 min: 25 °C at 10%, 30% and
50% RH.
Sunwoo et al. (2006a) Saccharin mucociliary clearance time, hydration state of skin, transdermal water
loss were measured in non-smoking male students. Rating of dryness and comfort.
Experimental conditions:
16 students 23 ± 3 The eyes and the skin become dry below 30% RH; below 10% RH nasal dryness as well as eyes
and skin. 10% RH, but not 30%, decreases saccharin mucociliary clearance time.
Skin hydration state affected at 10% and 30% RH, only.
(continued on next page)
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
384
Table 4 (continued)
Study Approach Number of
subjects
Age
years
Observation
Precondition: 25 °C/50% RH (50 min); exposure for 120 min: 25 °C at 10%, 30% and
50% RH.
Zhao et al. (2011) Nasal patency was rated by subjects (n = 44) when breathing under controlled
conditions from 3 different boxes:
Room air 24 °C, 49% RH
Dry air 25 °C, 27% RH
Cold air 12 °C. 59% RH
20 males
24 females
Both temperature and humidity contributed significantly to the perception of nasal patency
rating. Nasal mucosal cooling (heat loss) is the underlying stimulus in the individual’s
perception of patency and trigeminal input.
cHH = controlled heated breathing tube humidifier. PV = personal ventilation. T = temperature.
Table 5
Human chamber studies and sleep quality.
Study Approach Number of
subjects
Age
years
Observation
Nilius et al.
(2008)
Patients (n = 19) with obstructive sleep apnea. Effect of controlled heated breathing tube
humidifier (cHH) on nasal symptoms and quality of life during continuous positive airway
pressure.
14 male
5 female
55 ± 10 cHH improves subjective rating of nasal and pharyngeal symptoms (dry nose, dry mouth, dry
throat) during continuous positive airway pressure. After 4 weeks at home the use of cHH
also showed lower symptoms, but no effect was seen on sleep quality.
In summary, cHH improves side effects (symptoms) of continuous positive airway pressure,
but not quality of life, cf. (Ruhle et al., 2011). cHH might be beneficial for patients preferring
a cool bedroom temperature.
Nilius et al.
(2016)
Patients with obstructive sleep apnea were divided in high risk complaint group (n = 35)
and low risk complaint group (n = 37). Effect of controlled heated humidification on nasal
symptoms, improvement of sleep, quality of life during continuous positive airway pressure.
72 52 ± 8 Heated humidification in breathing air showed a positive effect by reduction of nasal
symptoms, and improvement of sleepiness and quality of life among the high-risk complaint
group.
Ryan et al.
(2009)
Patients with obstructive sleep apnea syndrome exposed to dry air, humidified air with or
without nasal steroid application in nasal continuous positive airway pressure therapy for 4
weeks.
125 Humidified air decreased the reported frequency of nasal symptoms in unselected
obstructive sleep apnea syndrome patients (28%), but not in the other groups; compliance,
sleepiness, and quality of life remained unchanged.
cHH = controlled heated breathing tube humidifier.
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
385
influence of humidity and associated mechanisms of infection, cf. Yang
and Marr (2012);Yang et al. (2012), especially in the field. Jaakkola
et al. (2014) hypothesized that “Higher temperature approaching 0 °C
may favor transmission and survival of the virus itself, but a decline in
temperature and humidity may make the host more susceptibility
through body cooling and/or drying of the respiratory tract”.Itis
suggested the combination relatively warmer temperature and higher
AH followed by a sudden decline in these meteorological parameters
have the strongest impact on the risk of influenza”. Air-conditioned
cold and dry air in offices, thus would favor survival and transmission
for certain airborne viruses, but not others (Morawska, 2006;Tang,
2009;Teller, 2009).
For bacteria, the situation about survival and transmission is even
more complex than viruses, thus, likewise requiring individual assess-
ment (Tang, 2009).
3.5. Vocal cord effects
Table 7 shows studies about effects on the vocal cord by humidity.
Desiccating challenge may be detrimental to voice production in in-
dividuals with vocal fatigue, even in young and vocally healthy males
(Hemler et al., 1997;Tanner et al., 2016); further, it has been shown
that isotonic saline nebulization decreases the self-perceived effort
among the males (Tanner et al., 2016). However, extended daily ex-
posure to high RH should be considered cautiously, because it may for
still unknown reason increase the risk of respiratory symptoms
(Angelon-Gaetz et al., 2015); this, in contrast to the positive observa-
tions about improved sleep quality, see above. Teachers’asthma-like
symptoms increased modestly, but not significantly, at both low and
high RH in schools (Angelon-Gaetz et al., 2016).
Overall, there are indications that both too high or too low RH may
be associated with adverse effects of virus survival and asthma-like
Table 6
Survival of influenza virus.
Study Approach Observation
Jaakkola et al.
(2014)
Case cross-over study among military conscripts (n = 892); 66 influenza A
(57) and B (9) episodes −in a cold climate.
“The risk of contracting influenza was positively associated with mean T and
AH. A decrease in both temperature and AH (max change) during the three
days prior to seeking medical consultation increased the risk of influenza”.
“According to these results, a 1 °C decrease and 0.5 g/m
3
decrease in AH
increased the estimated risk by 11% (OR1.11; 95%, CI 1.03–1.20)”.
Khare and Marr
(2015)
Model study of resuspension of dust and influenza virus. “Shorter people (children) may be more exposed to higher levels of
resuspended particulate matter than would taller ones”. It is hypothesized
that “particle resuspension could be a mode of disease transmission”.
Koep et al. (2013) Automated sensors for humidity and CO
2
levels in two schools and
humidification. Estimation of virus survival.
Strong association between outdoor and indoor AH. Estimated decrease of
virus survival at elevated AH. “Classroom humidification may be an
approach to increase indoor AH to levels that may decrease influenza virus
survival and transmission”.
Lowen et al.
(2007)
Influenza virus transmission studied in guinea pigs as model host in
environmental chamber at different temperature and RH.
Both cold temperature (5 °C) and dry conditions (20%) favor spreading of
influenza virus (transmission), while no transmission at 30 °C and 35% RH or
80% RH.
Transmission efficiency depends on RH and is inversely correlated with
temperature. Transmission sensitivity to RH is largely due to virus stability.
Cold temperature does not appear to impair the innate immune response.
Hypotheses about mechanisms in variation in transmission:
1. Breathing dry air may desiccate nasal mucosa, leading to epithelial
damage and/or reduced clearance, render the host more susceptible to
virus infection.
2. Stability of virus in aerosols shown to be maximal at low (20–40% RH) and
minimal at 50%, and high at 60–80% RH. Stability appears to be a key
determinant (except at high RH where transmission is absent).
3. Low RH enhances evaporation from exhaled bioaerosols leading to small
droplet nuclei that remain airborne for extended period, thus increasing
the opportunity for transmission of pathogens; conversely, high RH causes
water uptake in droplet nuclei, increase in size and increase of deposition.
Mäkinen et al.
(2009)
Population study (n = 892) where diagnosed respiratory tract infections
were compared with outdoor temperature and RH.
Cold outdoor temperature and low RH were associated with increased
occurrence of respiratory tract infection. Upper tract infection was associated
with AH and 1 g/m
3
of AH increased the risk of infections by 10%. A
decrease in temperature and RH preceded the onset of infection.
Myatt et al. (2010) Model study of survival of aerosolized virus in single-family residences by
moisture control. Estimation of emission rates for virus was particle specific.
Sleep quality included tidal breathing and coughing.
Output of 0.16 kg/h water increased median sleeping hours AH/RH levels of
11–19% compared to without a humidifier present. The associated decrease
in influenza virus survival was 17–32%. Distribution of water through a
whole residence increased RH 3–12% and reduced influenza virus survival
8–14%.
Noti et al. (2013) Infectivity of aerosolized virus was studied in a chamber with a manikin and
a coughing simulator emitting influenza virus.
The infectivity was ca. 75% at RH ≤23%, but only 15–22% at RH ≥43%.
“Maintaining indoor air at RH > 40% will significantly reduce the
infectivity of aerosolized virus”.
Shaman and Kohn
(2009)
Reanalysis of previous studies. AH provides a coherent physical explanation for variability of influenza virus
survival and transmission. The transmission of virus decreases with vapor
pressure.
Silva et al. (2014) Correlation of 11953 hospitalizations (adults and children) with respiratory
symptoms.
22% of infections in adult patients admitted to emergency departments were
caused by respiratory viral infections. Influenza-like illness was associated
with AH, use of air conditioning, and presence of mold in home. “Severe
acute respiratory infection cases were found to be negatively related to RH.”
Ud-Dean (2010) Model work and prediction of survival (persistence) and transmission of
influenza virus.
Example shows that “at lower temperature low AH prevents disruption of the
virus. On the other hand, higher temperature and higher RH prevent
desiccation of the virus”.
AH = absolute humidity. RH = relative humidity.
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
386
symptoms. This should be seen in view some of the reported beneficial
effects of reduced virus survival at elevated humidity in contrast to dry
and cold conditions; however, generalization is not possible. There are
anecdotal reports about “dry air”and problems among art performers
(e.g. singers); however, the few studies (Table 7) identified indicate that
extreme dry conditions may be detrimental in conjunction with vocal
fatigue and saline nebulization may be beneficial. It should be con-
sidered that vocal comfort among young healthy subjects may differ
from elderly subjects. Furthermore, other pollutants, e.g. with de-
siccating properties, should be considered.
4. Discussion and conclusion
Reporting of “dry air”or “dryness”continues to be a major com-
plaint in office-like environments, e.g. (Bluyssen et al., 2016;Brightman
et al., 2008;Reijula and Sundman-Digert, 2004) and anecdotal reports
about detrimental voice performance in dry conditions flourish in the
artistic milieu. This is surprising in view of the continued effort to de-
velop and use low emitting building materials and consumer products
during the last decades, e.g. by implementation of national labeling
schemes for emission testing (Wolkoff, 2003), a change to lower room
concentrations of VOCs by lower material emissions (Tuomainen et al.,
2003), and use of less volatile organic compounds (Weschler, 2009), if
the complaints are associated with indoor VOCs, as re-advocated by
Sundell and Lindvall (1993) and Fang et al. (2004). For instance, Qian
et al. (2016) argued that parents’perception of both dry and humid air
is associated with the presence of sensory irritants, especially dry air,
despite an organ of sensing humidity by inhalation is non-existing in
humans (Nagda and Rector, 2003;Wolkoffand Kjærgaard, 2007). Thus,
from a semantic point of view “dry air”or “humid air”, that is different
from the symptom “sensing of dryness”(e.g. dry eyes), appears to be
composed of different perceptions and associated causes, e.g. rhinitis
sicca (Hildenbrand et al., 2011). Further, it is unclear whether per-
ceived “humid or wet air”could be confused by the body sensation of
feeling humid (sweaty). Trigeminal nerve endings are known to re-
spond to innocuous cooling via activation of TRPM8 receptors
(Lumpkin and Caterina, 2007).
The Qian et al. study does not present data nor RH measurements
that support their statement about “dry air”(versus “humid air”) caused
by sensory irritants. From a toxicological point of view, however, re-
ported concentrations of VOCs in both office and residential environ-
ments, in general, are orders of magnitude below thresholds for sensory
irritation in the eyes and airways, perhaps with the exceptions of for-
maldehyde and acrolein (e.g., Huang et al., 2017), known emitters from
construction products, combustion, and ozone-initiated reactions
(Salthammer et al., 2010).
The prevalence of “dry air”more than doubled from one-man cel-
lular office to open space office; further, both eye and nose irritation
doubled (Pejtersen et al., 2006). Pejtersen et al. conclude: “It seems that
perceived dry air is something different from humidity and there is a
need to validate this question”and Wiik (2011) conclude “real cause of
the sensation of dry air is dusty air”. One may speculate about the
sensation of odor (pungent or moldy) might trigger the sensation of
“dry air”, possibly in concert with the physiological effects of low RH on
the eyes and upper airways. Further, unrecognized pollutants could
play a role by themselves or in (synergistic) combination with the
former loads, also see below. Furthermore, if the “sense of dryness”is
caused by stimulation of trigeminal nerve endings, it is fair to speculate
that irritated or dry eyes may cross interact with nerve endings from the
nose and vice versa, cf. Baroody et al. (2008). On the other hand,
several epidemiologic studies have shown associations between low RH
and complaint rates and intervention studies have demonstrated the
beneficial effect of elevating the humidity (Table 1). Furthermore, ag-
gravation of the eye tear film stability by exposure to low RH results in
desiccation, hyperosmolarity and inflammatory reactions in the eye
(Table 2 and Wolkoff(2017)). Thus, the merged information about the
impacts of VOCs and particles versus low RH favors the latter as an
important parameter to consider for assessment of eye and upper
airway complaints in office-like environments.
The overall mechanistic picture is that dry (and cold) air desiccate
the airways leading to hyperosmolarity, which stimulates the sensory
nerves generating a reflex response and possibly release of in-
flammatory biomarkers (Cruz and Togias, 2008). Further, dry air
challenge may increase peripheral airway resistance, airway surface
volume, and increase the osmolarity in the airways, which may initiate
airway constriction in canine, in case of no moisture neutralization
(Freed and Davis, 1999), and reduced mucociliary clearance time. This
may cause dryness of the mucocilia thus compromising its defense
mechanism from influenza virus, which for influenza viruses and others
has a greater survival time at low humidity and low temperature.
Furthermore, the defense mechanism may also be compromised by
aggressive air pollutants.
Synergistic effects may occur between low RH and air pollutants.
For instance, in a large cross-sectional study low RH and ozone were
associated with dry eye symptoms and dry eye diseases (Huang et al.,
2016). Further, evaporative dry eye rats were shown to be more sus-
ceptible to titanium dioxide nanoparticles than normal rats (Han et al.,
2017). It is reasonable to hypothesize that low RH has aggravated the
eye tear film stability, thus becoming more susceptible to aggressive
chemicals like ozone or its reaction products with chemically reactive
VOCs or particles. Surface active compounds like benzalkonium
chloride and particles like quartz may also cause compositional changes
of mucus membranes (Zhao and Wollmer, 2001), thus becoming more
susceptible to low RH and aggressive pollutants and mimic “dry air”.
In conclusion, elevated RH may reduce complaint rates and favor
work performance in offices in comparison with very dry conditions,
but more information is needed to understand how humidity influences
symptom reporting and the performance, especially among the elderly
Table 7
Effects on the vocal cord and voice.
Study Approach Observation
Hemler et al. (1997) Subjects (n = 8) exposed to different RH, dry (2%), normal (45%), and high
(100%) for 10 min at 23–24 °C. Analysis of voice perturbation during
producing repeatedly a sustained/a/of controlled pitch and loudness.
Dry conditions increased voice perturbation compared to normal and humid
air. No difference was observed between normal and humid air exposure.
Sivasankar et al.
(2008)
Subjects (n =8) reporting vocal fatigue and (n = 8) matched controls were
tested. Phonation threshold pressure was measured during oral breathing in
humid environments.
Drying challenge may be detrimental to voice production in individuals with
vocal fatigue. It is suggested that short-term oral breathing may cause
dehydration to impair compensation.
Tanner et al. (2016) Young (n =10; 22 years) male singers and male non-singers (n = 10)
underwent double-blinded exposure to oral breathing laryngeal desiccation
challenge for 30 min using medical grade dry air (< 1% RH) followed by
nebulized isotonic saline (3 or 9 ml).
Self-perceived effort and dryness increased (worsened) after challenge and
decreased after the saline nebulization. No consistent changes were
observed for phonation threshold pressure and cepstral spectral index of
dysphonia for sustained vowels and connected speech, self-perceived vocal
effort, mouth and throat dryness. Young, vocally healthy men may not
experience physiologic changes in voice production associated with
laryngeal desiccation.
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
387
population. Low RH aggravates the eye tear film stability and phy-
siology, and the osmolarity of the upper airways; even slightly elevated
humidity may be beneficial and relieve dry eye symptoms. Thus, per-
sonal adjustment of humidity and temperature appears to be the way
forward towards a satisfactory workplace. Furthermore, elevated hu-
midity may improve sleep quality and reduce effects on the vocal cord,
but more substantiation is required. Low and cold RH favors the sur-
vival and transmission of many influenza viruses, but the issue is
complex for generalization of associated mechanisms, thus, more con-
trolled indoor field experiences is warranted. Furthermore, better un-
derstanding is required how humidity influences particle dynamics,
resuspension, and their physiological impact on the eyes and the air-
ways as function of their surface chemistry.
There is an increasing trend to apply AH rather than RH as a
parameter for comparison and identification of associations, also con-
sidering sometimes better correlation between outdoor and indoor AH
than between RHs. However, most of all, it is pertinent to distinguish
between elevated moisture (activity) in construction materials and
behind, elevated RH resulting in condensation on surfaces, and RH in
the breathing and ocular zone. Furthermore, there is a need to re-
consider the causes and physiological meaning of the semantic in-
correct and confusing dry/wet air parameter by identification of its
causalities.
Declaration of interest
The author declares no conflicts of financial interest. No-one has
seen the manuscript before submission.
Acknowledgement
This work was supported by an internal grant from the National
Research Centre for the Working Environment Denmark and in part by
Realdania under the project CISBO (Centre for Indoor Climate and
Diseases in Dwellings, 2009–2015).
References
Abelson, R., Lane, K.J., Rodriguez, J., Johnson, P., Angjeli, E., Ousler, G., Montgomery,
D., 2012. A single-center study evaluating the effect of the controlled adverse en-
vironment (CAE
SM
) model on tear film stability. Clin. Ophtalmol. 6, 1865–1872.
Abusharna, A.A., Pearce, E.I., 2013. The effect of low humidity on the tear film. Cornea
32, 429–434.
Alex, A., Edwards, A., Hays, J.D., Kerkstra, M., Shih, A., Paiva, C.S., Pflugfelder, S.C.,
2013. Factors predicting the ocular surface response to desiccating environmental
stress. Invest. Ophthalmol. Vis. Sci. 54, 3325–3332.
Angelon-Gaetz, K.A., Richardson, D.B., Lipton, D.M., Marshall, S.W., Lamb, B., LoFrese,
T., 2015. The effects of building-related factors on classroom relative humidity
among north carolina schools participating in the free to breathe, free to teach study.
Indoor Air 25, 620–630.
Angelon-Gaetz, K.A., Richardson, D.B., Marshall, S.W., Hernandez, M.L., 2016.
Exploration of the effects of classroom humidity levels on teachers' respiratory
symptoms. Int. Arch. Occup. Environ. Health 89, 729–737.
Arundel, A.V., Sterling, E.M., Biggin, J.H., Sterling, T.D., 1986. Indirect health effects of
relative humidity in indoor environments. Environ. Health Perspect. 65, 351–361.
Atkinson, R., Arey, J., 2003. Gas-phase tropospheric chemistry of biogenic volatile or-
ganic compounds: a review. Atmos. Environ. 37, S197–S219.
Azuma, K., Ikeda, K., Kagi, N., Yanagi, U., Osawa, H., 2015. Prevalence and risk factors
associated with nonspecific building-related symptoms in office employees in Japan:
relationships between work environment, indoor air quality, and occupational stress.
Indoor Air 25, 499–511.
Azuma, K., Ikeda, K., Kagi, N., Yanagi, U., Osawa, H., 2017. Evaluating prevalence and
risk factors of building-related symptoms among office workers: seasonal character-
istics of symptoms and psysocoal and physical environmental factors. Environ. Health
Prev. Med. 22, 38.
Bakke, J.V., Moen, B.E., Wieslander, G., Norbäck, D., 2007. Gender and the physical and
psychosocial work environment are related to indoor air symptoms. J. Occup.
Environ. Med. 49, 641–650.
Bakke, J.V., Norbäck, D., Wieslander, G., Hollund, B.-E., Florvaag, E., Haugen, E.N.,
Moen, B.E., 2008. Symptoms, complaints, ocular and nasal physiological signs in
university staffin relation to indoor environment –temperature and gender inter-
actions. Indoor Air 18, 131–143.
Barabino, S., Shen, L., Chen, L., Rashid, S., Rolando, M., Dana, M.R., 2005. The con-
trolled-environment chamber: a new mouse model of dry eye. Invest. Ophthalmol.
Vis. Sci. 46, 2766–2771.
Baroody, F.M., Foster, K.A., Markaryan, A., de Tineo, M., Naclerio, R.M., 2008. Nasal
ocular reflexes and eye symptoms in patients with allergic rhinitis. Ann. Allergy.
Asthma. Immunol. 100, 194–199.
Bhangar, S., Adams, R.I., Pasut, W., Huffman, J.A., Arens, E.A., Taylor, J.W., Bruns, T.D.,
Nazaroff, W.W., 2016. Chamber aerosol study: human emissions of size-resolved
fluorescent biological aerosol particles. Indoor Air 26, 193–206.
Bluyssen, P.M., Roda, C., Mandin, C., Fossati, S., Carrer, P., de Kluizenaar, Y., Mihucz,
V.G., De Olivera Fernandes, E., Bartzis, J., 2016. Self-reported health and comfort in
‘Modern' office buildings: first results from the European OFFICAIR study. Indoor Air
26, 298–317.
Bottcher, R.W., 2001. An environmental nuisance: odor concentrated and transported by
dust. Chem. Senses 26, 327–331.
Brasche, S., Bullinger, M., Petrovitch, A., Mayer, E., Gebhardt, H., Herzog, V., Bischof, W.,
2005. Self-reported eye symptoms and related diagnostic findings –comparison of
risk factor profiles. Indoor Air 15 (Suppl. 15), 56–64.
Brightman, H.S., Milton, D.K., Wypij, D., Burge, H.A., Spengler, J.D., 2008. Evaluating
building-related symptoms using the US EPA BASE study results. Indoor Air 18,
335–345.
Cain, W.S., Schmidt, R., Leaderer, B.P., Gent, J.F., Bell, D., Berglund, L.G., 2002. Emission
of VOCs from materials used in buildings: analytical and sensory aspects. ASHRAE
Trans. 180, 283–296.
Callado, J.L.A., Varela, H.V., 2008. Study of olfactory function for pyridine in healthy
population: influence of variations in humidity. Acta Otorrinolaringol. Esp. 59,
475–479.
Chen, W., Zhang, X., Zhang, J., Chen, J., Wang, S., Wang, Q., Qu, J., 2008. Murine model
of dry eye induced by an intelligently controlled environmental system. Invest.
Ophthalmol. Vis. Sci. 49, 1386–1391.
Cruz, A.A., Togias, A., 2008. Upper airway reactions to cold air. Curr. Allergy Asthma
Rep. 8, 111–117.
Davis, R.E., McGregor, G.R., Enfield, K.B., 2016a. Humidity: a review and primer on at-
mospheric moisture and human health. Environ. Res. 144, 106–116.
Davis, R.E., Dougherty, E., McArthur, C., 2016b. Cold, dry air is associated with influenza
and pneumonia mortality in Auckland, New Zealand. Influenza Other Respir Viruses
10, 310–313.
Derby, M.M., Hamehkasi, M., Eckels, S., Hwang, G.M., Jones, B., Maghirang, R., Shulan,
D., 2016. Update of the scientific evidence for specifying lower limit relative hu-
midity levels for comfort, health, and indoor environmental quality in occupied
spaces (RP-1630). Sci. Technol. Built Environ. 23, 30–45.
Doty, R.L., Cometto-Muñiz, J.E., Jalowayski, A.A., Dalton, P., Kendall-Reed, M., Hodgson,
M., 2004. Assessment of upper respiratory tract and ocular irritative effects of volatile
chemicals in humans. Crit. Rev. Toxicol. 34, 85–142.
Fadeyi, M.O., Tham, K.W., Wu, W.Y., 2015. Impact of asthma, exposure period and filters
on human responses during exposures to ozone and its initiated chemistry products.
Indoor Air 25, 512–522.
Fang, L., Clausen, G., Fanger, P.O., 1998. Impact of temperature and humidity on the
perception of indoor air quality. Indoor Air 8, 80–90.
Fang, L., Clausen, G., Fanger, P.O., 1999. Impact of temperature and humidity on che-
mical and sensory emissions from building materials. Indoor Air 9, 193–201.
Fang, L., Wyon, D.P., Clausen, G., Fanger, P.O., 2004. Impact of indoor air temperature
and humidity in an office on perceived air quality, SBS symptoms and performance.
Indoor Air 14, 74–81.
Fanger, P.O., 2000. Indoor air quality in the 21 st century: search for excellence. Indoor
Air 10, 68–73.
Fechter, J.-O., Englund, F., Lundin, A., 2006. Association between temperature, relative
humidity and concentration of volatile organic compounds from wooden furniture in
a model room. Wood Mater. Sci. Eng. 1, 69–75.
Freed, A.N., Davis, M.S., 1999. Hyperventilation with dry air increases airway surface
fluid osmolarity in canine peripheral airways. Am. J. Respir. Crit. Care Med. 159,
1101–1107.
Fromme, H., Twardella, D., Dietrich, S., Heitmann, D., Schierl, R., Liebl, B., Rüden, H.,
2007. Particulate matter in the indoor air of classrooms-Exploratory results from
Munich and surrounding area. Atmos. Environ. 41, 854–866.
Galor, A., Kumar, N., Feuer, W., Lee, D.J., 2014. Environmental factors affect the risk of
dry eye syndrome in a United States veteran population. Ophthalmology 121,
972–973.
Gonzales-García, M.J., Gonzales-Sátz, A., de la Fuente, B., Morillo-Grasa, A., Mayo-Iscar,
A., San-José, J., Feijó, J., Stern, M.E., Calonge, M., 2007. Exposure to a controlled
adverse environment impairs the ocular surface of subjects with minimally sympto-
matic dry eye. Invest. Ophthalmol. Vis. Sci. 48, 4026–4032.
Han, Y.L., Hu, Y.M., Qian, F.P., 2011. Effects of air temperature and humidity on particle
deposition. Chem. Eng. Res. Des. 89, 2063–2069.
Han, J.Y., Kang, B., Eom, Y., Song, J.-S., 2017. Comparing the effects of particulate matter
on the ocular surface of normal eyes and a dry eye rat model. Cornea 36, 605–610.
Hanes, L.S., Issa, E., Proud, D., Togias, A., 2006. Stronger nasal responsiveness to cold air
in individuals with rhinitis and asthma, compared with rhinitis alone. Clin. Exp.
Allergy 36, 26–31.
Hansen, J.S., Nørgaard, A.W., Koponen, I., Sørli, J.B., Paidi, M.D., Clausen, P.A., Nielsen,
G.D., Wolkoff, P., Larsen, S.T., 2016. Limonene and its ozone-Initiated reaction
products attenuate lung inflammation in mice. J. Immunotoxicol. 13, 793–803.
Hashiguchi, N., Hirakawa, M., Tochihara, Y., Kaji, Y., Karaki, C., 2008. Effects of setting
up humidifiers on thermal conditions and subjective responses of patients and staffin
a hospital during winter. Appl. Ergon. 39, 158–165.
Hashiguchi, N., Takeda, A., Yasuyama, Y., Chishaki, A., Tochihara, Y., 2013. Effects of 6-h
exposure to low relative humidity and low air pressure on body fluid loss and blood
viscosity. Indoor Air 23, 430–436.
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
388
Hemler, R., Wieneke, G., Dejonckere, P., 1997. The effect of relative humidity of inhaled
air on acoustic parameters of voice in normal subjects. J. Voice 11, 295–300.
Hildenbrand, T., Weber, R.K., Brehmer, D., 2011. Rhinitis sicca, dry nose and athropic
rhinitis: a review of the literature. Eur. Arch. Otorhinolaryngol. 268, 17–26.
Hirayama, M., Murat, D., Liu, Y., Kojima, T., Kawakita, T., Tsubota, K., 2013. Efficacy of a
novel moist cool air device in office workers with dry eye disease. Acta Ophthalmol.
91, 756–762.
Huang, S., Xiong, J., Cai, C., Xu, C., Zhang, Y., 2016. Influence of humidity on the initial
emittable concentration of formaldehyde and hexaldehyde in building materials:
experimental observation and correlation. Sci. Rep. 6 (23388), 1–9.
Huang, S., Wei, W., Weschler, L.B., Salthammer, T., Kan, H., Bu, Z., Zhang, Y., 2017.
Indoor formaldehyde concentrations in urban China: preliminary study of some im-
portant influencing factors. Sci. Total Environ. 590 (591), 394–405.
Hurraß, J., Heinzow, B., Aurbach, U., Bergmann, K.C., Bufe, A., Buzina, W., Cornely, O.A.,
Engelhart, S., Fischer, G., Gabrio, T., Heinz, W., Herr, C.E.W., Kleine-Tebbe, J.,
Klimek, L., Köberle, M., Lichtnecker, H., Lob-Corzilius, T., Merget, R., Mülleneisen,
N., Nowak, D., Rabe, U., Raulf, M., Seidl, H.P., Steiß, J.O., Szewszyk, R., Thomas, P.,
Valtanen, K., Wiesmüller, G.A., 2017. Medical diagnostics for indoor mold exposure.
Int. J. Hyg. Environ. Health 220, 305–328.
Ikäheimo, T.M., Jaakkola, K., Jokelainen, J., Saukkoriipi, A., Roivainen, M., Juvonen, R.,
Vainio, O., Jaakkola, J.J., 2016. A decrease in temperature and humidity precedes
human rhinovirus infections in a cold climate. Viruses 8, E244.
Jaakkola, K., Saukkoriipi, A., Jokelainen, J., Juvonen, R., Kauppila, J., Vainio, O., Ziegler,
T., Rönkkö, E., Jaakkola, J.J.K., Ikäheimo, T.M., 2014. Decline in temperature and
humidity increases the occurrence of influenza in cold climate. Environ. Health
13, 22.
Kalhoff, H., 2003. Mild dehydration: a risk factor of broncho-pulmonary disorders. Eur. J.
Clin. Nutr. 57, S81–S87.
Keck, T., Leiacker, R., Heinrich, A., Kühnemann, S., Rettinger, G., 2000. Humidity and
temperature profile in the nasal cavity. Rhinology 38, 167–171.
Khare, P., Marr, L.C., 2015. Simulation of vertical concentration gradient of influenza
viruses in dust resuspended by walking. Indoor Air 25, 428–440.
Khosravi, M., Collins, P.B., Lin, R.-L., Hayes, D.J., 2014. Breathing hot humid air induces
airway irritation and cough in patients with allergic rhinitis. Reg. Physiol. Neurobiol.
198, 13–19.
Kim, D.-K., Rhee, K.-Y., Kwon, W.-K., Kim, T.-Y., Kang, J.-E., 2007. A heated humidifier
does not reduce laryngo-pharyngeal complaints after laryngeal mask anesthesia. Can.
J. Anesth. 54, 134–140.
Kivistö, T., Hakulinen, J., 1981. Der Staubgehalt Der Luft in Räumen Mit Textilen
Fussbodenbelägen. Staub –Reinhaltung der Luft Springer-Verlag 41, 357–358.
Koep, T.H., Enders, F.T., Pierret, C., Ekker, S.C., Krageschmidt, D., Neff, K.L., Lipsitch, M.,
Shaman, J., Huskins, W.C., 2013. Predictors of indoor absolute humidity and esti-
mated effects on influenza virus survival in grade schools. BMC Infect. Dis. 13, 71.
Korb, D.R., Blackie, C.A., 2013. Using goggles to increase periocular humidity and re-
ducedry eye symptoms. Eye Contact Lens 39, 273–276.
Kuehn, M., Welsch, H., Zahnert, T., Hummel, T., 2008. Changes of pressure and humidity
affect olfactory function. Eur. Arch. Otorhinolaryngol. 265, 299–302.
Kuwabara, Y., Alexeeff, G.V., Broadwin, R., Salmon, A.G., 2007. Evaluation and appli-
cation of the RD50 for determining acceptable exposure levels of airborne sensory
irritants for the general public. Environ. Health Perspect. 115, 1609–1616.
López-Miguel, A., Tesón, M., Martin-Montañez, V., Enriquez-de-Salamanca, A., Stern,
M.E., Calonge, M., Gonzales-García, M.J., 2014. Dry eye exacerbation in patients
exposed to desiccating stress under controlled environmental conditions. Am. J.
Ophthalmol. 157, 788–798.
Lan, L., Wargocki, P., Wyon, D.P., Lian, Z., 2011. Effects of thermal discomfort in an office
on perceived air quality, SBS, symptoms, physiological responses, and human per-
formance. Indoor Air 21, 376–390.
Larsen, S.T., Wolkoff, P., Hammer, M., Kofoed-Sørensen, V., Clausen, P.A., Nielsen, G.D.,
2013. Acute airway effects of airborne formaldehyde in sensitized and non-sensitized
mice housed in dry or humid environment. Toxicol. Appl. Pharmacol. 268, 294–299.
Li, W.L., Pauluhn, J., 2010. Comparative assessment of the sensory irritation potency in
mice and rats nose-only exposed to ammonia in dry and humid atmospheres.
Toxicology 276, 135–142.
Lin, R.-L., Hayes, D., Lee, L.-Y., 2009. Bronchoconstriction induced by hyperventilation
with humidified hot air: role of TRPV1-expressing airway afferents. J. Appl. Physiol.
106, 1917–1924.
Lindemann, J., Leiacker, R., Rettinger, G., Keck, T., 2003. The relationship between water
vapour saturation of inhaled air and nasal patency. Eur. Respir. J. 21, 313–316.
Lindgren, T., Norbäck, D., Wieslander, G., 2007. Perception of cabin air quality in airline
crew related to air humidification, on intercontinental flights. Indoor Air 17,
204–210.
Lipsitch, M., Viboud, C., 2009. Influenza seasonality: lifting the fog. PNAS 106,
3645–3646.
Lowen, A.C., Mubareka, S., Steel, J., Palese, P., 2007. Influenza virus transmission is
dependent on relative humidity and temperature. PLoS Pathog. 3, e151.
Lukcso, D., Guidotti, T.L., Franklin, D.E., Burt, A., 2016. Indoor environmental and air
quality characteristics, building-related health symptoms, and worker productivity in
a federal government building complex. Arch Env Occup Health 71, 85–101.
Lumpkin, E.A., Caterina, M.J., 2007. Mechanisms of sensory transduction in the skin.
Nature 445, 858–865.
Mäkinen, T.M., Juvonen, R., Jokelainen, J., Harju, T.H., Peitso, A., Bloigu, A.,
Silvennionen-Kassinen, S., Leinonen, M., Hassi, J., 2009. Cold temperature and low
humidity are associated with increased occurrence of respiratory tract infections.
Respir. Med. 103, 456–462.
Madden, L.C., Tomlinson, A., Simmons, P.A., 2013. Effect of humidity variations in a
controlled environment chamber on tear evaporation after dry eye therapy. Eye
Contact Lens 39, 169–174.
Markowicz, P., Larsson, L., 2015. Influence of relative humidity on VOC concentrations in
indoor air. Environ. Sci. Pollut. Res. 22, 5772–5779.
McFadden Jr., E.R., Nelson, J.A., Skowronski, M.E., Lenner, K.A., 1999. Thermally in-
duced asthma and airway drying. Am. J. Respir. Crit. Care Med. 160, 221–226.
Melikov, A.K., Skwarczynski, M.A., Kaczmarczyk, J., Zabecky, J., 2013. Use of persona-
lized ventilation for improving health, comfort, and performance at high room
temperature and humidity. Indoor Air 23, 250–263.
Memarzadeh, F., 2012. Literature review of the effect of temperature and humidity on
viruses. ASHRAE J. CH-12-029, 1049–1060.
Metz, J.A., Finn, A., 2015. Influenza and humidity –why a bit more damp may be good
for you!. J. Infect. 71, 554–558.
Monsé, C., Sucker, K., Hoffmeyer, F., Jettkant, B., Berresheim, H., Bünger, J., Brüning, T.,
2016. The influence of humidity on assessing irritation threshold for ammonia.
BioMed Res. Int. 2016, 6015761.
Morawska, L., 2006. Droplet fate in indoor environments, or can we prevent the spread of
infection? Indoor Air 16, 335–347.
Myatt, T.A., Kaufman, M.H., Allen, J.G., Macintosh, D.L., Fabian, M.P., McDevitt, J.J.,
2010. Modeling the airborne survival of influenza in a residential setting: the impacts
of home humidification. Environ. Health 9, 55.
Naclerio, R.M., Pinto, J., Assanasen, P., Baroody, F.M., 2007. Observations on the ability
of the nose to warm and humidify inspired air. Rhinology 45, 102–111.
Nagda, N.L., Hodgson, M., 2001. Low relative humidity and air cabin air quality. Indoor
Air 11, 200–214.
Nagda, N.L., Rector, H.E., 2003. A critical review of reported air concentrations of organic
compounds in aircraft cabins. Indoor Air 13, 292–301.
Nakamura, S., Kinoshita, S., Yokoi, N., Ogawa, Y., Shibuya, M., Nakashima, H., Hisamura,
R., Imada, T., Imagawa, T., Uehara, M., Shibuya, I., Dogru, M., Ward, S., Tsubota, K.,
2010. Lacrimal hypofunction As a new mechanism of dry eye in visual display
terminal users. PLoS One 5, e11119.
Nguyen, J.L., Schwartz, J., Dockery, D.W., 2014. The relationship between indoor and
outdoor temperature, apparent temperature, relative humidity, and absolute hu-
midity. Indoor Air 24, 103–112.
Nielsen, G.D., Wolkoff,P., 2017. Evaulation of airborne sensory irritants for setting ex-
posure limits or guidelines: a systematic approach. Regul. Toxicol. Pharmacol. 90,
308–317.
Nilius, G., Domanski, U., Franke, K.-F., Ruhle, K.-H., 2008. Impact of a controlled heated
breathing tube humidifier on sleep quality during CPAP therapy in a cool sleeping
environment. Eur. Respir. J. 31, 830–836.
Nilius, G., Franke, K.J., Domanski, U., Schroeder, M., Ruhle, K.-H., 2016. Effect of APAP
and heated humidification with a heated breathing tube on adherence, quality of life,
and nasopharyngeal complaints. Sleep Breath. 20, 43–49.
Norbäck, D., Wieslander, G., Nordström, K., Wålinder, R., Venge, P., 2000. The effect of
air humidification on symptoms and nasal patency, tear film stability, and biomarkers
in nasal lavage: A 6 weeks' longitudinal study. Indoor + Built Environ. 9, 28–34.
Norbäck, D., Lindgren, T., Wieslander, G., 2006. Changes in ocular and nasal signs and
symptoms among air crew in relation to air humidification on intercontinental
flights. Scand. J. Work. Environ. Health 32, 138–144.
Nordström, K., Norbäck, D., Akselsson, R., 1994. Effect of air humidification on the sick
building syndrome and perceived indoor air quality in hospitals: a four month
longitudinal study. Occup. Environ. Med. 51, 683–688.
Noti, J.D., Blachere, F.M., McMillen, C.M., Lindsley, W.G., Kashon, M.L., Slaughter, D.R.,
Beezhold, D.H., 2013. High humidity leads to loss of infectious influenza virus from
simulated coughs. PLoS One 8, e57485.
Ogawa, M., Dogru, M., Toriyama, N., Yamaguchi, T., Shimazaki, J., Tsubota, K., 2017.
Evaluation of the effect of moist chamber spectacles in patients with dry eye exposed
to adverse environment conditions. Eye Contact Lens. http://dx.doi.org/10.1097/
ICL.0000000000000431.
Paschides, C.A., Stefaniotou, M., Papageorgiou, J., Skourtis, P., Psilas, K., 1998. Ocular
surface and environmental changes. Acta Ophthalmol. Scand. 76, 74–77.
Pejtersen, J., Allerman, L., Kristensen, T.S., Poulsen, O.M., 2006. Indoor climate, psy-
chosocial work environment and symptoms in open-plan offices. Indoor Air 16,
392–401.
Philpott, C.M., Wolstenholme, C.R., Goodenough, P.C., Clark, A., Murty, G.E., 2007.
Which variables matter in smell tests in the clinic? J. Laryngol. Otol. 121, 952–956.
Qian, J., Ferro, A.R., 2008. Resuspension of dust particles in a chamber and associated
environmental factors. Aerosol Sci. Technol. 42, 566–578.
Qian, J., Peccia, J., Ferro, A.R., 2014. Walking-induced particle resuspension in indoor
environments. Atmos. Environ. 89, 464–481.
Qian, H., Zheng, X., Zhang, M., Weschler, L., Sundell, J., 2016. Associations between
parents' perceived air quality in homes and health among children in Nanjing, China.
PLoS One 11 (5), 1–12.
Reijula, K., Sundman-Digert, C., 2004. Assessment of indoor air problems at work with a
questionnaire. Occup. Environ. Med. 61, 33–38.
Reinikainen, L.M., Jaakkola, J.J., 2001. Efffects of temperature and humidification in the
office environment. Arch. Environ. Health 56, 365–368.
Reinikainen, L.M., Jaakkola, J.J.K., 2003. Significance of humidity and temperature on
skin and upper airway symptoms. Indoor Air 13, 344–352.
Reinikainen, L.M., Jaakkola, J.J.K., Seppänen, O., 1992. The effect of air humidification
on symptoms and perception of indoor air quality in office workers: a six-period
cross-over trial. Arch. Environ. Health 47, 8–15.
Reinikainen, L.M., Aunela-Tapola, L., Jaakkola, J.J.K., 1997. Humidification and per-
ceived indoor air quality in the office environment. Occup. Environ. Med. 54,
322–327.
Ruhle, K.-H., Franke, K.-F., Domanski, U., Nilius, G., 2011. Quality of life, compliance,
sleep and nasopharyngeal side effects during CPAP therapy with and without
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
389
controlled heated humidification. Sleep Breath. 15, 479–485.
Ryan, S., Doherty, L.S., Nolan, G.M., McNicholas, W.T., 2009. Effects of heated humidi-
fication and topical steroids on compliance, nasal symptoms, and quality of life in
patients with obstructive sleep apnea syndrome using nasal continuous positive air
airway pressure. J. Clin. Sleep Med. 15, 422–427.
Salah, B., Xuan, A.T.D., Fouilladieu, J.L., Lockhart, A., Regnard, J., 1988. Nasal muco-
ciliary transport in healthy subjects is slower when breathing dry air. Eur. Respir. J.
1, 852–855.
Salimifard, P., Rim, D., Gomes, C., Kremer, P., Freihaut, J.D., 2017. Resuspension of
biological particles from indoor surfaces: effects of humidity and air swirl. Sci. Total
Environ. 583, 241–247.
Salthammer, T., Mentese, S., Marutzky, R., 2010. Formaldehyde in the indoor environ-
ment. Chem. Rev. 110, 2536–2572.
Sato, M., Fukayo, S., Yano, E., 2003. Adverse environmental health effects of ultra-low
relative humidity indoor air. J. Occup. Health 45, 133–136.
Schaffer, F.L., Soergel, M.E., Straube, D.C., 1976. Survival of airborne influenza virus:
effects of propagating host, relative humidity, and composition of spray fluids. Arch.
Virol. 51, 263–273.
Shaman, J., Kohn, M., 2009. Absolute humidity modulates influenza survival, transmis-
sion, and seasonality. PNAS 106, 3243–3248.
Shaman, J., Pitzer, V.E., Viboud, C., Grenfell, B.T., Lipsitch, M., 2010. Absolute humidity
and the seasonal onset of influenza in the continental United States. PLoS Biol. 8,
e1000316.
Silva, D.R., Viana, V.P., Müller, A.M., Livi, F.P., Dalcin, P.D., 2014. Respiratory viral
infections and effects of meteorological parameters and air pollution in adults with
respiratory symptoms admitted to emergency rooms. Influenza Other Respir Viruses
8, 42–52.
Singh, M., Jaiswal, N., 2013. Dehumidifiers for Chronic Asthma (Review). The Cochrane
Library.
Sivasankar, M., Erickson, E., Schneider, S., Hawes, A., 2008. Phonatory effects of airway
dehydration: preliminary evidence of impaired compensation to oral breathing in
individuals with a history of vocal fatigue. J. Speech Lang. Hear. Res. 51, 1494–1506.
Suhalim, J.L., Parfitt, G.J., Xie, Y., de Pavia, C.S., Pflugfelder, S.C., Shah, T.N., Potma,
E.O., Brown, D.J., Jester, J.V., 2014. Effect of dessiccating stress on mouse meibo-
mian gland function. Ocul. Surf. 12, 59–68.
Sun, Y., Zhang, Y., Sundell, J., Fan, Z., Bao, L., 2009. Dampness in dorm rooms and its
association with allergy and airway infections among college students in China: a
cross-sectional study. Indoor Air 19, 348–356.
Sundell, J., Lindvall, T., 1993. Indoor air humidity and the sensation of dryness as risk
indicators of SBS. Indoor Air 3, 382–390.
Sunwoo, Y., Chou, C., Takeshita, J., Murakami, M., 2006a. Physiological and subjective
responses to low relative humidity. J. Physiol. Anthropol. 25, 7–14.
Sunwoo, Y., Chou, C., Takeshita, J., Murakami, M., Tochihara, Y., 2006b. Physiological
and subjective responses to low relative humidity in young and elderly men. J.
Physiol. Anthropol. 25, 229–238.
Takahashi, Y., Igaki, M., Sakamoto, I., Suzuki, A., Takahashi, G., Dogru, M., Tsubota, K.,
2010. Comparison of effects of periocular region dry and wet water on visual acuity
and near reflex. Nippon Ganka Gakkai Zasshi 114, 444–453.
Tang, J.W., 2009. The effect of environmental parameters on the survival of airborne
infectious agents. J. R. Soc. Interface 6 (6), S737–S746.
Tanner, K., Fujiki, R.B., Dromey, C., Merrill, R.M., Robb, W., Kendall, K.A., Hopkin, J.A.,
Chanell, R.W., Sivasankar, M.P., 2016. Laryngeal desiccation challenge and nebulized
isotonic saline in healthy male singers and nonsingers: effects on acoustic, aero-
dynamic, and self-perceived effort and dryness measures. J. Voice 30, 670–676.
Teller, R., 2009. Aerosol transmission of influenza a virus: a review of new studies. J. R.
Soc. Interface 6 (6), S783–S790.
Tesón, M., González-Garcia, M.J., López-Miguel, A., Enriquez-de-Salamanca, A., Martin-
Montañez, V., Benito, M.J., Mateo, M.E., Stern, M.E., Calonge, M., 2013. Influence of
a controlled environment simulating an in-flight airplane cabin on dry eye disease.
Invest. Ophthalmol. Vis. Sci. 54, 2093–2099.
Tian, Y., Sul, K., Qian, J., Mondal, S., Ferro, A.R., 2014. A comparative study of walking-
induced dust resuspension using a consistent test mechanism. Indoor Air 24,
592–603.
Trimble, M.W., Kaul, N., Wild, J.E., Bowman, J.P., 2007. The differences in human cu-
mulative irritation responses to positive and negative irritant controls from three
geographical locations. J. Cosmet. Sci. 58, 19–25.
Tuomainen, M., Tuomainen, A., Liesivuori, J., Pasanen, A.-L., 2003. The 3-year follow-up
study in a block of flats –experience in the use of the finnish indoor climate classi-
fication. Indoor Air 13, 136–147.
Uchiyama, E., Aronowicz, J.D., Butovich, I.A., McCulley, J.P., 2007. Increased evaportive
rates in laboratory testing conditions simulating airplane cabin relative humidity: an
important factor for dry eye syndrome. Eye Contact Lens 33, 174–176.
Ud-Dean, S.M.M., 2010. Structural explanation for the effect of humidity on persistence of
airborne virus: seasonality of influenza. J. Theoret. Biol. 264, 822–829.
Ugurlu, A.O., Esquinas, A.M., 2016. Effect of APAP and heated humidification with a
heated breathing tube on adherence, quality of life, and nasopharyngeal complaints.
Sleep Breath. 20, 251–252.
Um, S.-B., Kim, N.H., Lee, H.K., Song, J.S., Kim, H.C., 2014. Spatial epidemiology of dry
eye disease. Findings from South Korea. Int. J. Health Geogr. 13, 3–9.
Waduthantri, S., Tan, C.H., Fong, Y.W., Tong, L., 2015. Specialized moisture retention
eyewear for evaporative dry eye. Curr. Eye Res. 40, 490–495.
Walsh, N.P., Fortes, M.B., Raymond-Barker, P., Bishop, C., Owen, J., Tye, E.,
Esmaeelpour, M., Purslow, C., Elghenzai, S., 2012. Is whole body hydration an im-
portant consideration in dry eye? Invest. Ophthalmol. Vis. Sci. 53, 6622–6627.
Wang, M.T.M., Chan, E., Ea, L., Kam, C., Lu, Y., Misra, S.L., Craig, J.P., 2017. Randomized
trial of desktop humidifier for dry eye relief in computer users. Optom. Vis. Sci. 94,
1052–1057.
Weber, T.P., Stilianakis, N.I., 2008. Inactivation of influenza a viruses in the environment
and models of transmission. J. Infect. 57, 361–373.
Weschler, C.J., 2009. Changes in indoor pollutants since the 1950. Atmos. Environ. 43,
153–169.
Wiik, R., 2011. Indoor productivity measured by common response pattern to physical
and psychosocial stimuli. Indoor Air 21, 328–340.
Wilkins, C.K., Wolkoff, P., Clausen, P.A., Hammer, M., Nielsen, G.D., 2003. Upper airway
irritation of terpene/ozone oxidation products (TOPS). dependence on reaction time,
relative humidity and initial ozone concentration. Toxicol. Lett. 143, 109–114.
Williams, R., Rankin, N., Smith, T., Galler, D., Seakins, P., 1996. Relationship between the
humidity and temperature of inspired gas and the function of the airway mucosa.
Crit. Care Med. 24, 1920–1927.
Wolkoff, P., Kjærgaard, S.K., 2007. The dichotomy of relative humidity on indoor air
quality. Environ. Int. 33, 850–857.
Wolkoff, P., Clausen, P.A., Larsen, S.T., Hammer, M., Nielsen, G.D., 2012. Airway effects
of repeated exposures to ozone-initiated limonene oxidation products As model of
indoor air mixtures. Toxicol. Lett. 209, 166–172.
Wolkoff, P., 1998. Impact of air velocity, temperature, humidity, and air on long-term
VOC emissions from building products. Atmos. Environ. 32, 2659–2668.
Wolkoff, P., 2003. Trends in europe to reduce the indoor pollution of VOCs. Indoor Air 13,
5–11.
Wolkoff, P., 2013. Indoor air pollutants in office environments: assessment of comfort,
health, and performance. Int. J. Hyg. Environ. Health 216, 371–394.
Wolkoff, P., 2017. External eye symptoms in indoor environments. Indoor Air 27,
246–260.
World Health Organization, 2009. WHO Guidelines for Indoor Air Quality: Dampness and
Mould. WHO Regional Office for Europe, Copenhagen.
Wright, G.R., Howieson, S., McSharry, C., McMahon, A.D., Chaudhuri, R., Thompson, J.,
Donnelly, I., Brooks, R.G., Lawson, A., Jolly, L., McAlpine, L., King, E.M., Chapman,
M.D., Wood, S., Thomson, N.C., 2009. Effect of improved home ventilation on asthma
control and house dust mite allergen levels. Allergy 64, 1671–1680.
Wyon, D.P., Fang, L., Lagercrantz, L., Fanger, P.O., 2006. Experimental determination of
the limiting criteria for human exposure to low winter humidity indoors (RP-1160).
HVAC&R Res. 12, 201–213.
Xiao, B., Wang, Y., Reinach, P.S., Ren, Y., Li, J., Hua, S., Lu, H., Chen, W., 2015. Dynamic
ocular surface and lacrimal gland changes induced in experimental murine dry eye.
PLoS One 10, e0115333.
Yaglou, C.P., 1937. Physical and physiological principles of air conditioning. Part II.
JAMA 109, 945–950.
Yang, W., Marr, L.C., 2012. Mechanisms by which ambient humidity may affect viruses in
aerosols. Appl. Environ. Microbiol. 78, 6781–6788.
Yang, W., Elankumuran, S., Marr, L.C., 2012. Relationship between humidity and influ-
enza a viability in droplets and implications for influenza's seasonality. PLoS One 7,
e46789.
Yokoi, N., Uchino, M., Uchino, Y., Dogru, M., Kawashima, M., Komuro, A., Sonomura, Y.,
Kato, H., Tsubota, K., Kinoshita, S., 2015. Importance of tear film instability in dry
eye disease in office workers using visual display terminals: the Osaka study. Am. J.
Ophthalmol. 159, 748–754.
Zhang, H., Yoshino, H., 2010. Analysis of indoor humidity environment in chinese re-
sidential buildings. Build. Environ. 45, 2132–2140.
Zhao, J., Wollmer, P., 2001. Air pollutants and tear film stability –a method for ex-
perimental evaluation. Clin. Physiol. 21, 282–286.
Zhao, K., Blacker, K., Luo, Y., Bryant, B., Jiang, J., 2011. Perceiving nasal patency through
mucosal cooling rather than air temperature or nasal resistance. PLoS One 6, e24618.
Zhou, J., Fang, W., Cao, Q., Yang, L., Chang, V.W.C., Nazaroff, W.W., 2016. Influence of
moisturizer and relative humidity on human emissions of fluorescent biological
aerosol particles. Indoor Air 26, 587–598.
Zhou, C., Zhan, Y., Chen, S., Xia, M., Ronda, C., Sun, M., Chen, H., Shen, X., 2017.
Combined effects of temperature and humidity on indoor VOC pollution: intercity
comparison. Build. Environ. 121, 26–34.
P. WolkoffInternational Journal of Hygiene and Environmental Health 221 (2018) 376–390
390