When an odor triggers symptoms, does nasal inflammation change too?

For some people, exposure to chemical odors brings headaches, fatigue, nasal or throat discomfort, and other symptoms that interfere with everyday life. One proposed explanation is an excessive immune response in the upper airways, including the nose.

In a study published in 2015, Dantoft and colleagues compared people meeting criteria for multiple chemical sensitivity, or MCS, with healthy controls. They asked whether a situation in which odors triggered symptoms would also produce distinctive changes in inflammation-related substances on the surface of the nasal mucosa.

Exposing two groups of 18 to an odor under the same conditions

Participants were recruited through local advertisements and other channels in Sweden. The MCS group comprised 18 people meeting the study’s criteria, including symptoms lasting at least six months, symptoms triggered by exposure to several different chemicals, and improvement when the exposure ended. Substantial disruption to everyday life was also required.

There were also 18 healthy controls. These participants did not report symptoms or avoidance behavior associated with low concentrations of chemicals. Both groups were subject to exclusion criteria, including smoking, and were checked beforehand to ensure that they could detect the odor used.

The exposure was to a single substance, n-butanol, rather than a commercial perfume or detergent. It had been selected in preliminary testing as a stimulus capable of eliciting symptoms in people with MCS. Participants sat in a small chamber with a controlled concentration and underwent whole-body exposure to the airborne substance.

A detectable odor below the usual sensory irritation threshold

The target concentration was 3.7 ppm. The paper describes this as above the odor detection threshold but below sensory irritation thresholds reported in earlier research. That value does not guarantee that nobody will experience symptoms.

For the first ten minutes, no n-butanol was introduced, without informing the participants. The concentration was then raised gradually, reaching the target after approximately eight minutes, and maintained there for the remaining 42 minutes. The session lasted approximately one hour in total.

However, there was no separate session on another day presenting odorless air through the same procedure with participants unaware of which condition they received. An initial odorless period is not the same as an independent, blinded control condition.

Measuring 19 markers in fluid from the nasal surface

The research team placed small absorbent materials inside the nose to collect fluid from the mucosal surface. Samples were collected three times: before exposure, within 15 minutes after the session ended, and four hours after it ended. The 36 participants provided 108 samples in total. This does not mean that 108 people were studied.

The researchers measured 19 cytokines and chemokines. These substances convey information between immune-related cells or recruit cells, and include not only promoters of inflammation but also regulators of the response.

To account for differences in fluid volume and concentration, each marker was adjusted for the total protein in the sample. A feature of the study was that it examined substances involved in several immune responses together, rather than a single marker alone.

Symptoms differed, but no between-group difference in the markers was found

Symptoms and physiological responses from the same exposure experiment had already been reported in another paper. Compared with controls, the MCS group rated the odor as stronger and more unpleasant and reported more intense symptoms. Group differences in pulse and its variability were also reported. The present paper analyzed nasal samples from that experiment; it was not a replication in a different set of people.

For the 19 nasal markers, however, no statistically significant differences between groups were found before exposure. There were likewise no significant MCS-versus-control differences in any of the markers immediately after exposure or four hours later.

This does not mean that nothing changed over time. Some markers decreased at later time points in both groups. Overall, however, the findings did not indicate release of inflammation-related substances distinctive to the MCS group.

Which hypothesis did the findings help reassess?

The authors examined the explanation that excessive inflammation in the upper airways, including the nose, leads to systemic symptoms. Earlier studies had reported differences in certain immune-related substances in the blood of people with MCS. The question was also whether the upper airways might be their point of origin.

If large amounts of these substances were released in the nose and entered the blood or promoted systemic responses through another pathway, distinctive changes in nasal markers might be expected when symptoms occurred. Because no such between-group differences were found, the authors concluded that local upper-airway inflammation was not a well-supported explanation for symptoms under these conditions.

They also interpreted previously reported differences in blood markers as unlikely to be explained by excessive upper-airway inflammation as the starting point. However, the main measurements here were in nasal fluid. This study did not simultaneously measure blood changes and trace their origins.

The existence of symptoms and testing one mechanism are different questions

The findings do not mean that symptoms were absent. Indeed, symptom reports were stronger in the MCS group. Nor does the lack of between-group differences in the measured markers establish that all the symptoms have psychological causes.

The groups were small, with 18 participants each, and symptom responses varied between individuals. Nineteen markers measured at three sampling times may miss brief responses or changes involving other sites or substances. The study did not establish that the entire immune system was normal in every respect during measurement.

The authors also noted that an independent, blinded, odorless condition would have allowed closer examination of the effects of exposure itself versus anticipated discomfort or stress. Further research is needed to distinguish these mechanisms.

Moreover, a short exposure to one substance cannot be directly generalized to real perfumes, detergents, or environments containing chemical mixtures. This experiment does not determine the safety of a particular product or how an individual should be treated.

Conclusion

Even when n-butanol exposure elicited symptoms in people meeting the MCS criteria, no significant differences from healthy controls were found in the 19 nasal inflammation-related markers measured here. Having symptoms and confirming the proposed local inflammatory mechanism were not the same thing.

The significance is not a denial of symptoms, but a test of one possible explanation at a specific site using specific markers. The findings provide grounds for reassessing the idea that systemic responses begin with upper-airway inflammation and for investigating other pathways and conditions.

References

Dantoft, T. M., Skovbjerg, S., Andersson, L., Claeson, A.-S., Lind, N., Nordin, S., & Brix, S. (2015). Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity. PLOS ONE, 10(11), e0143534. DOI: 10.1371/journal.pone.0143534 / Full text. Original article license: CC BY.