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Relationship between exhaled nitric oxide and airway hyperresponsiveness following experimental rhinovirus infection in asthmatic subjects
Open accessAbstract
Exhaled nitric oxide (NO) is elevated in asthmatics, and varies with disease severity. We postulated that a respiratory virus infection increases exhaled NO levels in asthma, and examined the relationship between the virus-induced changes in exhaled NO and in airway hyperresponsiveness to histamine. In a parallel study, seven patients underwent experimental rhinovirus 16 (RV16) inoculation at days 0 and 1, whilst seven patients received placebo. Exhaled NO was measured at baseline (day 0) and at days 1, 2 and 3 after inoculation. Histamine challenges were performed prior to (day -7) and after inoculation (day 3), and were expressed as provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). Following RV16 infection there was a significant increase in NO at days 2 and 3 as compared to baseline (median change (range): 4.2 (7.5) parts per billion (ppb), p=0.03, and 3.0 (10.1) ppb, p=0.02, respectively). Furthermore, PC20 decreased significantly following RV16 infection (mean+/-SD change in doubling dose: -0.65+/-0.54, p=0.02), whereas PC20 did not change in the placebo group (p=0.1). There was a significant correlation between the RV16-induced changes in exhaled NO levels at day 2 and the accompanying changes in PC20 at day 3 (rank correlation coefficient (rs): 0.86, p=0.01). Hence, the greater the increase in exhaled NO, the smaller the decrease in PC20. We conclude that rhinovirus infection increases exhaled nitric oxide levels in asthmatics, and that this increase is inversely associated with worsening of airway hyperresponsiveness to histamine. These results suggest that viral induction of nitric oxide synthase within the airways may play a protective role in exacerbations of asthma.
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TLRs play a crucial role in the initiation of immune responses in the respiratory epithelium.
“TLRs play a crucial role in the initiation of immune responses in the respiratory epithelium (45, 175).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [45]
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Metadata
- Authors
- de Gouw, H., Grunberg, K., Schot, R., Kroes, A., Dick, E., & Sterk, P.
- ORCID
- Schot, R
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 1998-01-01
- Volume
- 11
- Issue
- 1
- Pages
- 126-132
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- OpenAlex
- W2138926811
- Cited by
- 167
- References
- 37
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 11 · 2013: 2 · 2012: 9
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Respiratory Journal (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- exhaled nitric oxide, airway hyperresponsiveness, rhinovirus infection, rhinovirus 16, asthma, histamine challenge, nitric oxide synthase, airway inflammation
- MeSH terms
- Adult, Aerosols, Asthma, Female, Forced Expiratory Volume, Histamine, Humans, Male, Nitric Oxide, Picornaviridae Infections, Respiration, Rhinovirus, Bronchial Hyperreactivity
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