Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms

Lehtimäki, Lauri; Kankaanranta, Hannu; Saarelainen, Seppo; Turjanmaa, Väinö; Moilanen, Eeva

doi:10.1183/09031936.02.00202002

Cited by 101 publications

(86 citation statements)

References 30 publications

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“…This could be due to differences between patient characteristics and/or differences in the technical aspects of the measurements, such as the use of higher flow rates to calculate alveolar NO in the present study. The alveolar NO levels in the current study were comparable to those of LEHTIMAKI and co-workers [23,24], who used the same flow rates and was the first to measure alveolar NO levels in patients with asthma. Comparison of alveolar NO levels between patients with mildto-moderate and severe asthma revealed no significant differences after initial analysis, which was surprising.…”

Section: Discussionsupporting

confidence: 73%

“…Comparison of alveolar NO levels between patients with mildto-moderate and severe asthma revealed no significant differences after initial analysis, which was surprising. In studies by other groups, higher levels of alveolar NO were found in symptomatic children versus asymptomatic children with asthma [22], in patients with nocturnal asthma compared with non-nocturnal asthma [23], and in patients with severe versus mild-to-moderate asthma [11]. An explanation for the lack of a significant difference in alveolar NO levels between patients with mild-to-moderate and severe asthma in the present study could be the large variability of alveolar NO levels amongst the patients with severe asthma.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Alveolar nitric oxideversusmeasures of peripheral airway dysfunction in severe asthma

Veen¹,

Sterk²,

Schot³

et al. 2006

Eur Respir J

129

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Alveolar nitric oxide (NO) is a measure of peripheral airway inflammation in asthma, potentially associated with disease severity. The relationship between alveolar NO and physiological tests of peripheral airway (dys)function has not been investigated. The present authors hypothesised that peripheral airway inflammation and dysfunction are inter-related and associated with asthma severity.Alveolar NO was compared between 17 patients with mild-to-moderate asthma and 14 patients with severe asthma and related to total lung capacity (TLC), residual volume (RV)/TLC, thoracic gas volume (FRC), slope of the single breath nitrogen washout curve (dN 2 ), closing capacity (CC)/ TLC and fall in forced vital capacity at the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second. In patients with severe asthma, strong correlations were found between alveolar NO and RV/TLC % pred, FRC % pred, dN 2 , and CC/TLC. Patients with oral steroid-dependent asthma had higher alveolar NO levels (2.7 ppb) compared with the other patients with severe (0.6 ppb) and mild-to-moderate asthma (0.3 ppb).The present authors conclude that alveolar nitric oxide is closely related to parameters of peripheral airway dysfunction in patients with severe asthma, and that oral steroid-dependent asthmatics have more peripheral airway disease than nonsteroid-dependent asthmatics. This suggests that patients on chronic oral steroid treatment have more extensive disease and require additional anti-inflammatory treatment to better target the peripheral airways.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Alveolar nitric oxideversusmeasures of peripheral airway dysfunction in severe asthma

Veen¹,

Sterk²,

Schot³

et al. 2006

Eur Respir J

129

View full text Add to dashboard Cite

show abstract

“…There was no difference in proximal airway inflammation assessed by sputum eosinophil count, single flow NO concentration or bronchial NO output, implying that the difference in alveolar NO concentration is due to the difference in the site rather than the intensity of the lower airway response. Nocturnal wheeze was reported by a similar proportion of patients in all asthma groups so the current authors' findings are unlikely to be due to differences in the prevalence of nocturnal asthma, a condition that has been associated with high alveolar NO concentrations [15]. Similarly, there was no relationship between asthma control, assessed using the Juniper asthma control score, at the time of sampling and alveolar NO concentration, suggesting that distal airway inflammation occurs in patients who require high doses of inhaled steroids or oral steroids to achieve control of their symptoms, as well as patients with uncontrolled asthma.…”

Section: Discussionmentioning

confidence: 72%

Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma

Berry

Hargadon²,

Morgan³

et al. 2005

European Respiratory Journal

202

136

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Recent studies have suggested that alveolar nitric oxide (NO) concentration is a noninvasive test of distal lung inflammation.The current study determined whether alveolar NO concentration can be measured in patients with asthma of varying severity, tested the hypothesis that there is an association between alveolar NO and bronchoalveolar lavage (BAL) eosinophil count and determined whether refractory asthma is characterised by a raised alveolar NO concentration. Finally, the present authors assessed the effect of 2 weeks of prednisolone (30 mg q.d.) on alveolar NO concentration.Alveolar NO concentration was both measurable and repeatable in patients with refractory asthma. A positive correlation was found between alveolar NO concentration and BAL eosinophil count but not with bronchial wash or sputum eosinophil count. Alveolar NO concentration was increased in patients with refractory asthma (7.1 ppb) compared with mildto-moderate asthma (3.4 ppb) and normal controls (3.4 ppb) and reduced by treatment with prednisolone.In conclusion, these findings support the hypothesis that alveolar nitric oxide is a measure of distal airway inflammation and suggest that distal lung inflammation is present in refractory asthma.

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“…Recently, methods for measuring eNO at multiple expiratory flows (MEFeNO) [13,14] have been used to detect elevated levels of alveolar NO in fibrosing alveolitis [13], asthma [15,16] and COPD [17] leading to the refinement of analytical methods to discriminate exhaled NO sources in the lung [18].…”

mentioning

confidence: 99%

Exhaled nitric oxide from lung periphery is increased in COPD

Brindicci¹

2005

European Respiratory Journal

181

159

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Single constant flow exhaled nitric oxide (eNO) cannot distinguish between the sources of NO. The present study measured eNO at multiple expired flows (MEFeNO) to partition NO into alveolar (Calv,NO) and bronchial (Jaw,NO) fractions to investigate peripheral lung contribution to eNO in chronic obstructive lung disease (COPD).MEFeNO were made in 81 subjects including 18 nonsmokers, 16 smokers and 47 COPD patients of different severity by the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD): 0 (n514), 1 (n57), 2 (n511), 3 (n58) and 4 (n57).COPD severity was correlated with an increased Calv,NO regardless of the patient's smoking habit or current treatment. The levels of Calv,NO (in ppb) were 1.4¡0.09 in nonsmokers, 2.1¡0.1 in smokers categorised as GOLD stage 0 (smokers-GOLD0), 3.3¡0.18 in GOLD1-2 and 3.4¡0.1 in GOLD3-4. Jaw,NO levels (pL?s -1 ) were higher in nonsmokers than smokers-GOLD0 (716.2¡33.3versus 464.7¡41.8), GOLD3-4 (609.4¡71). Diffusion of NO in the airways (Daw,NO pL?ppb -1 s -1 ) was higher (p,0.05) in GOLD3-4 than in nonsmokers (15¡1.2 versus 11¡0.5) and smokers-GOLD0 (11.6¡0.5). MEFeNO measurements were reproducible, free from day-to-day and diurnal variation and were not affected by bronchodilators.In conclusion, chronic obstructive pulmonary disease is associated with elevated alveolar nitric oxide. Measurements of nitric oxide at multiple expired flows may be useful in monitoring inflammation and progression of chronic obstructive pulmonary disease, and the response to anti-inflammatory treatment.KEYWORDS: Chronic obstructive pulmonary disease, exhaled nitric oxide, multiple expiratory flow, small airway inflammation S ingle expiratory flow exhaled nitric oxide (eNO) measurements are simple, highly reproducible [1], have been used to monitor larger airway inflammation in asthma research [2], and are now moving into clinical practice [3]. However, small airways and lung parenchyma are the predominant sites of inflammation in patients with chronic obstructive pulmonary disease (COPD) [4]. Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the small airway wall by inflammatory cells [4]. There is a high level of expression of inducible NO synthase (iNOS) presence in sputum macrophages [5], alveolar walls, small airway epithelium and vascular smooth muscle of COPD patients [5,6]. In patients with COPD this may result in an increased production of NO and NO-related species in the lung periphery, which through the function of peroxynitrite may amplify the inflammation and lead to inhaled corticosteroid (ICS) resistance, particularly as the disease becomes more severe [7].The current single expiratory technique measures predominantly larger airway-derived NO and may only partially reflect peripheral inflammation [8,9]. eNO is often in the normal range or even reduced in moderate COPD [10], probably due to down-regulation of endothelial NO synthase (eNOS) [11] and iNOS [12] by cigarette ...

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Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms

Cited by 101 publications

References 30 publications

Alveolar nitric oxideversusmeasures of peripheral airway dysfunction in severe asthma

Alveolar nitric oxideversusmeasures of peripheral airway dysfunction in severe asthma

Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma

Exhaled nitric oxide from lung periphery is increased in COPD

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