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Indoor air humidity, air quality, and health – An overview

April 2018
International Journal of Hygiene and Environmental Health 221(3):376-390

DOI:10.1016/j.ijheh.2018.01.015

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National Research Centre for the Working Environment

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 environment; 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 obstructive 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, humidity, 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 perceptions 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 improvement 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.

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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

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

; 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

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

; 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

) 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

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.

Li and Pauluhn

(2010)

Mice and rat (male) bioassay. Animals (4 per condition) were exposed

to ammonia and respiratory rate RD

was measured.

Reduction of RD

(%)

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

) reduction by

exposure to ozone/limonene mixture (16 s old) and ozone/isoprene

mixture (90 s old) at diﬀerent RH.

Reduction of RD

(%)

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.

= concentration that causes 50% reduction of the respiratory rate.

* Statistically signiﬁcant.

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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

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.

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

) 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)

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

) 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

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

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

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

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).

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