Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance

Narang, Indra; Ersu, Refika; Wilson, Nicola; Bush, Andrew

doi:10.1136/thorax.57.7.586

Cited by 200 publications

(168 citation statements)

References 20 publications

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“…For the confirmed PCD group with defined ultrastructural defects in the ciliary axonemes, the mean nNO level (20.0 nl/ min) is less than 10% of the mean nNO measurement for healthy control subjects (304.6 nl/min) with minimal overlap. Previous reports in smaller subsets show a similar magnitude of difference between PCD and healthy control subjects (7)(8)(9)(10)(11)(12). The cutoff value defined in this study (77 nl/min) is slightly lower than what was identified in our earlier study that examined a smaller patient population (7).…”

Section: Original Researchmentioning

confidence: 57%

“…The nNO values in some of the patients with CF, however, did overlap with PCD values, which has been described in other studies (7)(8)(9)11). Therefore, CF must be excluded by a quantitative pilocarpine iontophoresis sweat test or CFTR genotype testing in all individuals with nNO measurements below the cutoff values.…”

Section: Original Researchmentioning

confidence: 80%

“…The American Thoracic Society (ATS), in cooperation with the European Respiratory Society (ERS), has published guidelines for nNO measurements, which recommend obtaining levels while the patient performs trained velum closure or exhales against resistance or other techniques to decrease dilution from the lower airways (15). Although several studies have demonstrated that nNO levels are significantly lower in PCD than those measured in healthy control subjects, these investigations had several limitations, including small numbers of PCD-affected subjects and few disease control subjects, and each of these single-site studies has used a different NO analyzer with different sampling flow rate and methodology, which restricts side-by-side comparisons to assess reproducibility at multiple sites with different operators (7)(8)(9)(10)(11)(12)(13). Further standardization is needed for its use as a test to support the clinical diagnosis of PCD.…”

mentioning

confidence: 99%

“…An alternative, reproducible, and cost-effective test would help direct appropriate individuals to further testing and potentially lead to earlier therapy. Studies have suggested that nasal nitric oxide (nNO) measurement could be a useful test for PCD (7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

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Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Leigh¹,

Hazucha²,

Chawla³

et al. 2013

Annals ATS

248

289

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Rationale: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized.Objectives: To use a standard protocol for measuring nNO to establish a diseasespecific cutoff value at one site, and then validate at six other sites.Methods: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. Measurements and Main Results:At the lead site, nNO values in PCD (mean 6 standard deviation, 20.7 6 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 6 118.8; 125.5-867.0 nl/min), asthma (267.8 6 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 6 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 6 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, .0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD.Conclusions: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.

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Section: Original Researchmentioning

confidence: 57%

Section: Original Researchmentioning

confidence: 80%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Leigh¹,

Hazucha²,

Chawla³

et al. 2013

Annals ATS

248

289

View full text Add to dashboard Cite

show abstract

“…For example, nasal NO is extremely low in primary ciliary dyskinesia (PCD) [4] and in cystic fibrosis [24]. In fact, a nasal NO test is currently part of the clinical routine at the national centre for PCD in the UK [25]. In allergic rhinitis the picture is less clear.…”

Section: Discussionmentioning

confidence: 97%

Assessment of nasal and sinus nitric oxide output using single-breath humming exhalations

Maniscalco¹,

Weitzberg²,

Sundberg³

et al. 2003

Eur Respir J

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Nasal nitric oxide (NO) levels increase greatly during humming compared to silent exhalation. In this study, the physiological and anatomical factors that regulate NO release during humming have been characterised in 10 healthy subjects and in a model of the sinus and the nose.Single-breath humming caused a large initial peak in nasal NO output, followed by a progressive decline. The NO peak decreased in a step-wise manner during repeated consecutive humming manoeuvres but recovered completely after a silent period of 3 min. Topical nasal application of an NO synthase inhibitor reduced nasal NO by w50% but had no effect on the increase evoked by humming. Silently exhaled nasal NO measured immediately after repeated humming manoeuvres was between 5-50% lower than basal silent NO exhalation, suggesting variable continuous contribution from the sinuses to nasal NO. Among the factors known to influence normal sinus ventilation, ostium size was the most critical during humming, but humming frequency was also of importance.In conclusion, humming results in a large increase in nasal nitric oxide, which is caused by a rapid gas exchange in the paranasal sinuses. Combined nasal nitric oxide measurement with and without humming could be of use to estimate sinus ventilation and to better separate nasal mucosal nitric oxide output from sinus nitric oxide in health and disease. Eur Respir J 2003; 22: 323-329. This study was supported by a grant from the Swedish Heart-Lung Foundation, the Swedish Research Council and by a grant from University Federico II "Progetto scambi internazionali".Nitric oxide (NO) is released into the airway lumen [1], in particular in the upper airways [2][3][4]. The exact origin of NO found in nasal air and the relative contribution from different sources within the nasal airways are not known. The paranasal sinuses are major sources of NO in adult healthy subjects [5] and the concentrations in a healthy sinus may be very high, ranging 5-20 parts per million (ppm) [5]. The sinuses communicate with the nasal cavity through the ostia and the rate of gas exchange between these cavities is dependent on several factors, such as the size of the ostia, the volume of the sinus, the nasal airflow and intra-nasal pressure [6,7]. Proper ventilation is essential for maintenance of sinus integrity, and blockage of the ostium is a central event in the pathogenesis of sinusitis [8,9]. During normal ventilation, the time required to exchange all air in the sinuses is y30 min, with large inter-individual variation [7,10]. Sinus ventilation is much slower in patients with sinus disorders [10].Recently, the current authors have shown that nasal NO levels increase greatly during humming compared to normal silent nasal exhalation, probably by speeding up the sinus gas exchange, thereby increasing nasal NO output [11]. In a twocompartment model of the nose and sinus the authors demonstrated that pulsating airflow, created by humming, causes a dramatic increase in gas exchange between these cavities [11].In the ...

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Exhaled Nitric Oxide in Acute Respiratory Syncytial Virus Bronchiolitis

Gadish

Soferman²,

Merimovitch³

et al. 2010

Arch Pediatr Adolesc Med

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Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance

Cited by 200 publications

References 20 publications

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Assessment of nasal and sinus nitric oxide output using single-breath humming exhalations

Exhaled Nitric Oxide in Acute Respiratory Syncytial Virus Bronchiolitis

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