Changes in exhaled carbon monoxide and nitric oxide levels following allergen challenge in patients with asthma

Abstract

Carbon monoxide is a product of haem degradation by haem oxygenase (HO), activated by inflammatory cytokines and oxidants. This study examined whether allergen challenge can increase exhaled CO levels, as a reflection of HO activation.Exhaled CO and nitric oxide, an expired gas also thought to reflect cytokine-induced airway inflammation, were measured in 15 atopic steroid-naive nonsmoking patients with asthma (13 males, aged 3062 yrs) before and for up to 20 h after allergen challenge.Baseline CO (4.40.3 parts per million (ppm)) and NO (20.661.2 parts per billion (ppb)) levels were elevated in asthmatic as compared with nonsmoking normal volunteers (n=37, 2.10.2 ppm and 7.00.1 ppb, respectively, p<0.05). In 10 patients with a dual response in the forced expiratory volume in one second (FEV1) there was a maximal increase in exhaled CO at 1 h (34.37.1%) and at 6 h (6912%, p<0.01), followed by a maximal fall in FEV1 (289%, p<0.05) at 9 h, whereas the maximal NO increase was observed at 10 h (50.211.8%). The maximal increase in exhaled CO in single response patients (n=5) was 302% during the early asthmatic reaction and 46.3 9.2% between 4 and 10 h, followed by a fall in FEV1 (93%, p>0.05) at 9 h, whereas exhaled NO was not significantly changed. In five patients exhaled CO was not attenuated by inhalation of increasing concentrations of histamine causing a 20% fall in FEV1 (PC20) or its subsequent relief by b 2 -agonists.In conclusion, exhaled carbon monoxide is increased during the early and late asthmatic reactions independently of the change in airway calibre, while exhaled nitric oxide is increased only during the late reaction and follows the increase in carbon monoxide and fall in the forced expiratory volume in one second in time. Eur Respir J 1999; 13: 48±52. There is considerable evidence for airway inflammation and oxidative stress in patients with asthma, even when the disease is mild [1,2]. Bronchoalveolar lavage (BAL) and bronchial biopsy studies have demonstrated the infiltration of activated inflammatory cells in the airway mucosa and there is a broad relationship between the intensity of inflammation and the clinical severity of asthma. Inhalation of allergen provides a model of asthmatic inflammation, as it provokes an early fall in forced expiratory volume in one second (FEV1) owing to the release of bronchoconstrictor mediators, such as histamine, leukotrienes and prostaglandins [3], and a late asthmatic response which is associated with a prolonged bronchoconstriction, influx of inflammatory cells [4] and mediators [5±7] and an increase in the oxidative stress in the airway.It is becoming clear that some oxidant-induced mediators and enzymes, such as haem oxygenase (HO), may also play a vital role in the airway protective response to oxidative stress. Two isoforms of HO have been described: the constitutive HO-2, which is highly expressed in the brain and testes, and the inducible HO-1, which is ubiquitously distributed. The latter is activated by a variety of pro-inflammatory cytoki...

Exhaled Nitric Oxide Levels After Specific Inahalatory Challenge Test in Subjects with Diagnosed Occupational Asthma

“…These results are consistent with earlier reports showing elevated eNO levels after allergen challenges at the time of the late response [21][22][23]. It is unlikely that our NO measurements could be partly affected by NO derived from nasal cavities by diffusion.…”

Exhaled nitric oxide in specific challenge tests to assess occupational asthma

“…eNO has been found to correlate with the number of eosinophils and the level of eosinophilic cationic protein in induced sputum, indicating that eNO specifically reflects eosinophilic inflammation [8][9][10]. After allergen challenges, elevated eNO levels have been reported at the time of the late response [11][12][13].…”

Oxidative Damage and Bronchial Asthma

“…HO-1 is activated by a lots of inflammatory mediators, reactive oxygen species and by another stimuli (proinflammatory cytokines: interleukin-1 , interleukin-6, interferon-, tumor necrosis factor-, bacterial toxins; airway viral infection; heme; hemin; reactive oxygen species: superoxide, peroxynitrite, hydrogen peroxide and reactive nitrogen species) (Nath et al, 2001;Sardana et al, 1981). HO-1 is expresses mainly in epithelial cells and endothelial cells of air system (Paredi et al, 1999).…”

“…Heme oxygenase (heat shock protein 32, HO; EC 1.14.99.3) plays an important role in organism defence to oxidative stress (Paredi et al, 1999) and inflammation (Otterbien & Choi, 2000). There are known tree isoforms of HO: HO-1, HO-2, and HO-3.…”