Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis

Our plain-English summary of Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis, by H. Lehtonen, P. Oksa, L. Lehtimäki, et al (Thorax, 2007).

The study

• Authors: H. Lehtonen, P. Oksa, L. Lehtimäki, A. Sepponen, R. Nieminen, H. Kankaanranta, S. Saarelainen, R. Järvenpää, J. Uitti, E. Moilanen
• Journal: Thorax
• Published: 2007;62(7):602-7
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Inhaled asbestos fibres can cause inflammation and fibrosis in the lungs called asbestosis. However, there are no non-invasive means to assess and follow the severity of the inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess the alveolar NO concentration and bronchial NO flux, which reflect inflammation in the lung parenchyma and airways, respectively. The aim of the present study was to investigate whether exhaled NO or markers in exhaled breath condensate could be used to assess inflammation in asbestosis.

Methods: Exhaled NO and inflammatory markers (leukotriene B(4) and 8-isoprostane) in exhaled breath condensate were measured in 15 non-smoking patients with asbestosis and in 15 healthy controls. Exhaled NO concentrations were measured at four constant exhalation flow rates (50, 100, 200 and 300 ml/s) and alveolar NO concentration and bronchial NO flux were calculated according to the linear model of pulmonary NO dynamics.

Results: The mean (SE) alveolar NO concentration was significantly higher in patients with asbestosis than in controls (3.2 (0.4) vs 2.0 (0.2) ppb, p = 0.008). There was no difference in bronchial NO flux (0.9 (0.1) vs 0.9 (0.1) nl/s, p = 0.93) or NO concentration measured at ATS standard flow rate of 50 ml/s (20.0 (2.0) vs 19.7 (1.8) ppb, p = 0.89). Patients with asbestosis had increased levels of leukotriene B4 (39.5 (6.0) vs 15.4 (2.9) pg/ml, p = 0.002) and 8-isoprostane (33.5 (9.6) vs 11.9 (2.8) pg/ml, p = 0.048) in exhaled breath condensate and raised serum levels of C-reactive protein (2.3 (0.3) vs 1.1 (0.2) mug/ml, p = 0.003), interleukin-6 (3.5 (0.5) vs 1.7 (0.4) pg/ml, p = 0.007) and myeloperoxidase (356 (48) vs 240 (20) ng/ml, p = 0.034) compared with healthy controls.

Conclusions: Patients with asbestosis have an increased alveolar NO concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath. Measurement of exhaled NO at multiple exhalation flow rates and analysis of inflammatory markers in exhaled breath condensate are promising non-invasive means for assessing inflammation in patients with asbestosis.

In plain English

This study from Tampere, Finland, compared 15 non-smoking men with asbestosis with 15 age-matched healthy male volunteers. The patients had been exposed to asbestos for an average of 20.5 years, and their exposure had ended an average of 25.6 years earlier. The researchers measured nitric oxide (NO) in exhaled breath at four exhalation speeds. This let them estimate how much NO came from the air sacs (alveolar) and how much from the airways (bronchial). They also tested condensed breath and blood for markers of inflammation. Average alveolar NO was higher in the patients (3.2 vs 2.0 ppb, p=0.008). Bronchial NO and the standard single-speed NO test did not differ between the groups. The patients' breath condensate had higher leukotriene B4 (39.5 vs 15.4 pg/ml) and 8-isoprostane (33.5 vs 11.9 pg/ml). Their blood had higher C-reactive protein, interleukin-6 and myeloperoxidase. The authors noted that the group was relatively small and that one lung measurement was estimated rather than measured. They concluded that these breath tests are promising non-invasive ways to assess lung inflammation in asbestosis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cross-sectional comparison of patients with asbestosis and age- and sex-matched healthy controls (exhaled breath, breath condensate and blood measurements)
• Who was studied: 15 men with asbestosis (mean age 67, range 56 to 74), recruited from patient records of Tampere University Hospital, Finland, and diagnosed before 2002. They were compared with 15 age-matched healthy male volunteers (mean age 63, range 53 to 73) with normal spirometry. All subjects were non-smokers, meaning they had quit at least 5 years earlier.
• Exposure: Asbestos exposure, with no fiber type specified. Patients had an average of 20.5 years of exposure (range 10 to 39), which had stopped an average of 25.6 years earlier. Diagnosis required moderate (10 to 25 fibre-years) or heavy (more than 25 fibre-years) exposure.
• Main results:
  • Mean (SE) alveolar NO concentration was higher in patients with asbestosis than in healthy controls: 3.2 (0.4) vs 2.0 (0.2) ppb, p=0.008.
  • Bronchial NO flux was the same in both groups: 0.9 (0.1) vs 0.9 (0.1) nl/s, p=0.93. Exhaled NO did not differ at 50, 100 or 200 ml/s; at 300 ml/s it tended to be higher in patients (p=0.06).
  • In exhaled breath condensate, patients with asbestosis had higher leukotriene B4 than controls, 39.5 (6.0) vs 15.4 (2.9) pg/ml, p=0.002. They also had higher 8-isoprostane, 33.5 (9.6) vs 11.9 (2.8) pg/ml, p=0.048.
  • Patients with asbestosis had higher serum levels than controls of C-reactive protein (2.3 (0.3) vs 1.1 (0.2), p=0.003), interleukin-6 (3.5 (0.5) vs 1.7 (0.4) pg/ml, p=0.007) and myeloperoxidase (356 (48) vs 240 (20) ng/ml, p=0.034).
  • The estimated rate of NO passing from lung tissue into the air sacs was higher in patients than in controls (4.1 (0.6) vs 3.1 (0.3) nl/s), but the difference was not statistically significant (p=0.13).
• The authors' conclusion: The authors concluded that patients with asbestosis have an increased alveolar NO concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath. In their view, multiple-flow exhaled NO measurement and breath condensate analysis are promising non-invasive means of measuring lung inflammation in asbestosis. They said further studies are needed to see whether these methods can track disease progression or response to treatment.
• Limitations the authors state:
  • The estimated NO production rate difference was not statistically significant in the relatively small group of patients.
  • The NO transfer factor was not measured. In patients it was estimated from the carbon monoxide transfer factor, and in healthy controls from population normal values.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Inflammation, Fibrosis, Parenchyma.

Related studies

• Increased 8-isoprostane, a marker of oxidative stress in exhaled breath condensate in subjects with asbestos exposure — D. Pelclová, Z. Fenclová, et al. (2008)
• Fractional exhaled nitric oxide concentration is increased in asbestosis and pleural plaques — A. Sandrini, A.R. Johnson, et al. (2006)
• Alveolar macrophages from patients with asbestos exposure release increased levels of leukotriene B4 — J.G. Garcia, D.E. Griffith, et al. (1989)
• Leukotrienes B4, C4, D4 and E4 in the exhaled breath condensate (EBC), blood and urine in patients with pneumoconiosis — D. Pelclová, Z. Fenclová, et al. (2012)
• Nitric oxide (NO) synthase activity in the lung and NO synthesis in alveolar macrophages of rats increased on exposure to asbestos — H. Iguchi, S. Kojo, et al. (1996)
• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)

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