Biomarkers of oxidative stress and antioxidants in severe asthma: A Prospective Case-Control Study.

BACKGROUND: Bronchial airway inflammation is the hallmark of asthma, which may be driven by an imbalance between oxidative stress and antioxidant defenses. Antioxidants deficiency may play a role, but this has remained unconfirmed. OBJECTIVE: To evaluate the oxidative stress burden and antioxidants defenses in patients with increasing asthma severity. METHODS: This prospective case-control study compared fractional exhaled nitric oxide (FeNO), exhaled breath condensate nitrite/nitrate (EBC-NOx), spirometry, and serum vitamins and trace elements among patients with and without asthma. RESULTS: Sixty participants were recruited (30 with severe asthma number; 23 women [76.7%]; mean age, 41.4 years; mean forced expiratory volume in 1 second [FEV1], 2.2 L [72.2% predicted]; mean inhaled corticosteroid dosage, 2,540 µg/d; 18/30 [60%] receiving maintenance oral corticosteroids; 15 with mild asthma; all corticosteroids naïve; 9 women [60%]; mean age, 34.6 years; mean FEV1, 3.48 L [100.5% predicted]; 15 healthy controls; 12 women [80%]; mean age, 37.6 years; and mean FEV1, 3.53 L [111.7% predicted]). The mean FeNO levels increased significantly with increasing asthma severity (P = .01), but the EBC-NOx levels did not change significantly (P = .90). Paradoxically, vitamin A and vitamin E increased with increased disease severity, with vitamin E levels increasing significantly (P = .07 and P < .001, respectively). There was no significant difference between groups in the levels of copper (P = .37), zinc (P = .97), or selenium (P = .90). CONCLUSION: FeNO but not EBC-NOx is increased significantly with asthma severity with no evidence of vitamins or trace elements deficiency in severe asthma. Impaired oxidative stress defenses in severe asthma may be driven by factors other than vitamins or trace elements deficiency.

Association between exhaled breath condensate nitrate + nitrite levels with ambient coarse particle exposure in subjects with airways disease.

OBJECTIVES: Studies of individual inflammatory responses to exposure to air pollution are few but are important in defining the most sensitive markers in better understanding pathophysiological pathways in the lung. The goal of this study was to assess whether exposure to airborne particles is associated with oxidative stress in an epidemiological setting. METHODS: The authors assessed exposure to particulate matter air pollution in four European cities in relation to levels of nitrite plus nitrate (NOx) in exhaled breath condensate (EBC) measurements in 133 subjects with asthma or chronic obstructive pulmonary disease using an EBC capture method developed for field use. In each subject, three measurements were collected. Exposure measurements included particles smaller than 10 µm (PM(10)), smaller than 2.5 µm (PM(2.5)) and particle number counts at a central site, outdoors near the subject's home and indoors. RESULTS: There were positive and significant relationships between EBC NOx and coarse particles at the central sampling sites (increase of 20.4% (95% CI 6.1% to 36.6%) per 10 µg/m(3) increase of coarse particles of the previous day) but not between EBC NOx and other particle measures. Associations tended to be stronger in subjects not taking steroid medication. CONCLUSIONS: An association was found between exposure to ambient coarse particles at central sites and EBC NOx, a marker of oxidative stress. The lack of association between PM measures more indicative of personal exposures (particularly indoor exposure) means interpretation should be cautious. However, EBC NOx may prove to be a marker of PM-induced oxidative stress in epidemiological studies.

Methacholine-induced asthma symptoms correlate with impulse oscillometry but not spirometry.

Previous studies showed poor correlation between asthma symptoms and spirometric-based bronchial provocation tests. Use of impulse oscillometry (IOS) in airways resistance measurement may be more sensitive. In 20 individuals with stable asthma, we analysed the relationship between methacholine-induced asthma symptoms scores, IOS and spirometry. Following a screening visit, methacholine challenge testing was performed twice (visits 1 and 2). Dyspnoea, tightness and wheeze were quantified using visual analogue scores. IOS and spirometry were conducted at each incremental dose of methacholine. The Pearson correlation coefficient and linear regression analyses were conducted to explore the relations. A significant correlation was observed between methacholine-induced dyspnoea scores and the change in IOS measures of R((5)) (r=0.62, p=0.004) and X(5) (r=0.51, p=0.022), but not with the spirometric changes in FEV((1)) (r=0.37(,)p=0.11) or MEF(50) (r=0.32, p=0.17). In a multiple linear regression model, R(5) was the only significant variable to explain dyspnoea variability (p=0.003). Results of correlation analyses for chest tightness were similar to those obtained with dyspnoea. However, the symptom of wheeze showed correlation with IOS and spirometry. We conclude that airway resistance measured by IOS during methacholine challenge correlates better with asthma symptoms than traditional spirometric measures implying a higher sensitivity index.

Changes in vagal tone with posture in asthma are related to changes in ventilatory pattern.

BACKGROUND: Posturally induced changes in minute ventilation in patients may be autonomically driven. This study aimed to test whether changes in autonomic tone with posture differed between normal and asthmatic subjects and whether this related to changes in indices of ventilation. METHODS: Ten patients with type 1 brittle asthma (BA), 10 with non-brittle, severe asthma (SA), 10 with mild asthma (MA) and 10 normal individuals were studied lying flat, at 60 degrees head up tilt and flat again each for 30min, assessing end-tidal CO(2) (ETCO(2)), respiratory rate and autonomic tone by heart rate variability. RESULTS: Parasympathetic tone (as high-frequency [HF] power) fell on tilt in all four groups, all showing increases in LF (low frequency)/HF ratio (sympatho-vagal balance) on tilt (BA, 2.03-4.9; SA, 3.3-8.2; MA, 1.5-4.9; normals, 2.3-6.6). ETCO(2) on tilt fell significantly in all 3 asthma groups (BA, DeltaETCO(2) -0.4, 95% CIs -0.18 to -0.75, P=0.005; SA, -0.7, 95% CIs -0.27 to -1.16, P=0.004; MA, -0.5, 95% CIs -0.14 to -0.78, P=0.01) but not in normals (-0.1, 95% CIs +0.23 to -0.49). The fall in ETCO(2) on tilt correlated with the fall in HF power in all three asthma groups but not in normal subjects. CONCLUSION: Changes in vagal tone posture are seen on tilt in both normal and asthmatic subjects which relate to changes in ETCO(2) only in asthmatic subjects. This provides support for the hypothesis that hyper-ventilatory response to postural change in asthma is autonomically influenced.