Nitric Oxide and Proinflammatory Cytokines in Nasal Lavage Fluid Associated with Symptoms and  Exposure to Moldy Building Microbes

Hirvonen, Maija-Riitta; Ruotsalainen, Marjo; Roponen, Marjut; Hyvärinen, Anne; Husman, Tuula; Kosma, Veli‐Matti; Komulainen, Hannu; Savolainen, Kai; Nevalainen, Aino

doi:10.1164/ajrccm.160.6.9903023

Cited by 79 publications

(79 citation statements)

References 23 publications

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“…Moreover, all except two of the atopic subjects were taking medication for either rheumatic or respiratory diseases, which may have influenced the level of the production of the cytokines in this group. These results support earlier findings suggesting that occupational exposure in a mould-damaged building leads to increased production of inflammatory mediators in the upper airways of exposed occupants [2].…”

Section: Discussionsupporting

confidence: 92%

“…In the present study, employees with prolonged respiratory symptoms or rheumatic disease and their reference subjects reported the same kind of symptoms, as observed earlier in an epidemiological study of people living or working in moisture-damaged buildings [1]. They did, however, report more skin and eye symptoms than employees of a school with a mouldy building in a previous study [2]. During the vacation, all of the reported symptoms diminished, indicating that they were related to workplace exposure.…”

Section: Discussionsupporting

confidence: 86%

“…This view is supported by the authors9 recent results showing an association between increased production of inflammatory markers in the nasal lavage (NAL) fluid, the high prevalence of respiratory symptoms in occupants, and chronic indoor exposure to microbes [2]. There are also case reports linking environmental exposure and a cluster of various inflammatory rheumatic diseases in a mould-damaged building [3].…”

mentioning

confidence: 85%

“…NAL was performed as previously described [2]. Briefly, 4.5 mL prewarmed Hank9s balanced salt solution (HBSS; Gibco, Paisley, UK) (37uC) was instilled into the nostril through a heat softened catheter.…”

Section: Nasal Lavagementioning

confidence: 99%

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Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders

Roponen

Seuri

et al. 2001

Eur Respir J

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Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders. M. Roponen, J. Kiviranta, M. Seuri, H. Tukiainen, R. Myllykangas-Luosujärvi, M-R. Hirvonen. #ERS Journals Ltd 2001. ABSTRACT: Exposure to microbes present in mould-damaged buildings has been linked to increased frequency of various inflammatory diseases. The current study examined differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS) and serum of occupants with rheumatic or respiratory disorders and their controls, all working in the same moisture-damaged building.Exhaled nitric oxide (NO) measurements, lung function tests, skin-prick tests and health data collection by questionnaire were performed. Concentrations of NO, interleukin (IL)-1, IL-4, IL-6 and tumour necrosis factor-a in NAL, IS and serum (excluding NO and IL-1) of the subjects were measured during an occupational exposure period and the vacation period without such exposure.The concentrations of IL-4 in NAL fluid were significantly higher among all occupants during the working period (geometric mean 8.5 pg?mL -1 , range 0-206.5 pg?mL -1 ), as compared to that during vacation (0.4 pg?mL -1 , range 0-3.7 pg?mL -1 ) (p=0.008). Absence from the work environment also significantly diminished reporting of symptoms. IL-4 levels in the serum of case subjects were significantly higher than in controls. Moreover, employees with respiratory symptoms had markedly higher exhaled NO values than their controls (p=0.028).In summary, these data suggest that mediators in nasal lavage samples reflect the occupational exposure to moulds, whereas possible indicators of existing disorders are detectable in serum.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 85%

Section: Nasal Lavagementioning

confidence: 99%

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Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders

Roponen

Seuri

et al. 2001

Eur Respir J

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“…These cytokines are of interest in searching for new diagnostic tools because of their central role in airway inflammation. They may be involved in allergic inflammation as well as in symptoms caused by occupational or indoor air exposures [18].…”

Section: ) Reproducibility Of Measurements Is Expressed As Proposementioning

confidence: 99%

Reproducibility of measurements of exhaled NO, and cell count and cytokine concentrations in induced sputum

Purokivi

Randell

Hirvonen³

et al. 2000

Eur Respir J

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Reproducibility of measurements of exhaled NO, and cell count and cytokine concentrations in induced sputum. M. Purokivi, J. Randell, M-R. Hirvonen, H. Tukiainen. #ERS Journals Ltd 2000. ABSTRACT: Sputum induction is a noninvasive, well-tolerated method for studying airway inflammation. When induction with hypertonic saline is repeated at short time-intervals (<24 h), the cell profile of sputum has not been reproducible. To determine the proper interval between sampling cell profiles and cytokine contents of sputum samples that had been induced 48 h apart, were compared. In addition, the inducible nitric oxide synthase (iNOS) expression of sputum cells was compared to the levels of exhaled nitric oxide (NO).Sputum induction and measurement of exhaled NO was performed in 31 healthy nonatopic volunteers. Cell differentials were counted. Concentrations of interleukin (IL)-4, IL-6, tumour necrosis factor (TNF)a, eosinophil cationic protein (ECP) were measured in sputum supernatant, and iNOS was determined.Reproducibility of cell counts was high (r=0.836 total cells, r=0.762 neutrophils, r=0.966 eosinophils, r=0.742 macrophages). IL-4 (r=0.398), IL-6 (r=0.566), TNFa (r=0.658) and ECP (r=0.501) were also less reproducible in healthy volunteers. Consistent with the low levels of NO in the exhaled air (18.52.6 ppb and 19.32.8 parts per billion (ppb) on the two study days, r=0.976, p=0.0000), expression of iNOS was not detected.In conclusion, in healthy subjects, induced sputum cell counts are reproducible. Even though the success rate in nonatopic populations is relatively low, sputum induction appears to be a valid method for detecting inflammatory changes within the airways, when being performed 48 h apart. Eur Respir J 2000; 16: 242±246. There has been wide interest in developing noninvasive methods to determine lower airway inflammation in different respiratory disorders. Measurement of inflammatory mediators in induced sputum provides a direct method to investigate airway inflammation in different respiratory conditions including asthma. Sputum induction by nebulized hypertonic saline has been found to be safe and well tolerated [1±3]. However, the saline inhalation affects the production of inflammatory markers, since neutrophilia and loss of macrophages has been reported in samplings repeated within 24 h [4]. This suggests that a longer time interval is required between two samplings of induced sputum, when it is used for the evaluation of allergen challenge. Thus, the time interval in which possible effects of saline inhalation disappear, needs to be defined.Defining the cytokine profile in induced sputum could widen the view to inflammatory state of lower respiratory tract. Previously the attempts to measure cytokines by using bronchoalveolar lavage samples have failed because of dilution caused by the large volume of saline needed for sampling [5]. In sputum induction this problem is avoided, at least when low volume of nebulized saline is used [6].Since not all patients are able to produce sputum, despite ind...

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Multiple Chemical Sensitivity: Toxicological Questions and Mechanisms

Pall

2009

General, Applied and Systems Toxicology

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Cases of multiple chemical sensitivity (MCS) are initiated by exposure to organic solvents and three classes of pesticides. Each of these can act indirectly to increase NMDA activity and the toxic effects of members of each of these classes can be lowered by using NMDA antagonists. Other chemicals, mercury, H 2 S and CO exposure may also initiate cases of MCS and have toxic responses mediated through increased NMDA activity. Thus each of these types of chemicals appears to act as a toxicant through increased NMDA activity. Six additional types of evidence suggest roles for elevated NMDA activity in MCS, suggesting that this response is involved, not only in MCS case initiation, but also in response to low‐level chemicals in those who are already sensitive. The inference that chemicals act as toxicants in MCS is confirmed by three genetic studies showing that five genes that encode enzymes that metabolize these chemicals act to determine MCS susceptibility. The chronic nature of MCS is thought to be produced by a local biochemical vicious cycle mechanism, the NO/ONOO − cycle, which is initiated by nitric oxide acting through its oxidant product peroxynitrite, which are both produced in MCS in response to excessive NMDA activity. Cycle elements, including NMDA activity, intracellular calcium, nitric oxide and peroxynitrite are thought to interact with other mechanisms, including neural sensitization in the brain and neurogenic inflammation in peripheral tissues to produce the high‐level chemical sensitivity that is the hallmark of MCS. This complex model of MCS is supported by the following types of observations: MCS correlates in the chronic phase of illness, extensive animal model studies implicating almost all NO/ONOO − cycle elements, clinical trial data in the related illnesses chronic fatigue syndrome and fibromyalgia, and a variety of objectively measurable responses to low‐level chemical exposure in MCS patients, responses that should be further studied as possible specific biomarker tests for MCS. While plausible mechanisms are proposed for the generation of both shared and specific symptoms and signs in MCS, there are little data on whether these mechanisms are actually involved in generating these symptoms and signs in MCS. Previous claims that MCS is produced by some sort of psychogenic mechanism have multiple flaws and are inconsistent with the various types of evidence discussed above. Several areas of research are discussed in which the author argues that research will be richly rewarded.

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Nitric Oxide and Proinflammatory Cytokines in Nasal Lavage Fluid Associated with Symptoms and Exposure to Moldy Building Microbes

Cited by 79 publications

References 23 publications

Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders

Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders

Reproducibility of measurements of exhaled NO, and cell count and cytokine concentrations in induced sputum

Multiple Chemical Sensitivity: Toxicological Questions and Mechanisms

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