Reproducibility of measurements of exhaled NO, and cell count and cytokine concentrations in induced sputum

Purokivi, Minna; Randell, Jukka; Hirvonen, M.-R.; Tukiainen, H

doi:10.1034/j.1399-3003.2000.16b10.x

Cited by 34 publications

(28 citation statements)

References 20 publications

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“…Therefore, sputum induction should not be repeated frequently. An interval of 48 h between two inductions gave reproducible cell counts in normal subjects [39]. More research is needed to determine the minimum interval required between repeated inductions in order to ensure that "carry-over" effects are avoided.…”

Section: Frequency Of Sputum Inductionmentioning

confidence: 99%

Sputum induction

Chanez¹,

Holz²,

Ind³

et al. 2002

European Respiratory Journal

119

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The aim of sputum induction is to collect an adequate sample of secretions from lower airways in subjects who do not produce sputum spontaneously in order to study the features of airway inflammation in asthma and other respiratory disorders. Inhalation of isotonic or hypertonic solutions administered by nebulisation has been demonstrated to induce a small amount of airway secretion that can be expectorated and analysed. The mechanisms by which this occurs are not known, but both direct and indirect mechanisms are likely to be involved. It is believed that the increased osmolarity of the airway lining fluid increases vascular permeability in the bronchial mucosa and induces production of mucus by submucosal glands. Animal studies have shown that hypertonic saline increases vascular permeability in the airways, and this effect can be modulated by capsaicin [1]. However, in vivo instillation of hypertonic solution into the airways of animals and humans induces an increase in the levels of several mediators but no rise in levels of albumin or other markers of increased vascular permeability [2,3]. Therefore, this hypothesis has not been confirmed, and only preliminary measurements of sputum osmolarity after induction have been reported with conflicting results [4]. Conversely, previous reports have demonstrated increased clearance of secretions from the airways in humans after administration of hypertonic saline aerosol [5], perhaps by facilitating the collection of small amounts of pre-existing airway secretions.Although sputum induction has been used extensively since the 1990s, few methodological studies have examined the influence of various technical factors on the feasibility and repeatability of sputum induction and collection. As with other techniques, the lack of a "gold standard" makes it hard to evaluate the influence of these technical factors on the adequacy and accuracy of sputum induction.The technique of sputum induction consists of inhaling an aerosol of saline (either normal or hypertonic) over different time-periods. Volunteers/ patients are instructed to expectorate into a container. Various issues must be considered with regard to this procedure: 1) facilities, equipment and personnel; 2) bronchodilator pretreatment; 3) pulmonary function monitoring; 4) concentration of saline solution and nebuliser output; 5) duration of inhalation; 6) expectoration technique; 7) spontaneous versus induced sputum; and 8) frequency of sputum induction. The influence of these factors on the feasibility of the technique must be evaluated in terms of the success rate, repeatability and accuracy of the results obtained.

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Section: Frequency Of Sputum Inductionmentioning

confidence: 99%

Sputum induction

Chanez¹,

Holz²,

Ind³

et al. 2002

European Respiratory Journal

119

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“…Exhaled NO was measured by a chemiluminescence analyser (Sievers Model 280 NOA, Sievers Instruments Inc., Boulder, CO, USA) according to European Respiratory Society guidelines [16], as described earlier [12]. Briefly, subjects performed a slow vital capacity manoeuvre for 30 s against a fixed expiratory resistance.…”

Section: Measurement Of Exhaled Nitric Oxidementioning

confidence: 99%

“…IS collection was performed as described earlier [12]. Briefly, the sputum was induced with inhalation of ultrasonically nebulized hypertonic (3%) saline.…”

Section: Induced Sputum Collectionmentioning

confidence: 99%

Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders

Roponen

Seuri

et al. 2001

Eur Respir J

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Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders. M. Roponen, J. Kiviranta, M. Seuri, H. Tukiainen, R. Myllykangas-Luosujärvi, M-R. Hirvonen. #ERS Journals Ltd 2001. ABSTRACT: Exposure to microbes present in mould-damaged buildings has been linked to increased frequency of various inflammatory diseases. The current study examined differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS) and serum of occupants with rheumatic or respiratory disorders and their controls, all working in the same moisture-damaged building.Exhaled nitric oxide (NO) measurements, lung function tests, skin-prick tests and health data collection by questionnaire were performed. Concentrations of NO, interleukin (IL)-1, IL-4, IL-6 and tumour necrosis factor-a in NAL, IS and serum (excluding NO and IL-1) of the subjects were measured during an occupational exposure period and the vacation period without such exposure.The concentrations of IL-4 in NAL fluid were significantly higher among all occupants during the working period (geometric mean 8.5 pg?mL -1 , range 0-206.5 pg?mL -1 ), as compared to that during vacation (0.4 pg?mL -1 , range 0-3.7 pg?mL -1 ) (p=0.008). Absence from the work environment also significantly diminished reporting of symptoms. IL-4 levels in the serum of case subjects were significantly higher than in controls. Moreover, employees with respiratory symptoms had markedly higher exhaled NO values than their controls (p=0.028).In summary, these data suggest that mediators in nasal lavage samples reflect the occupational exposure to moulds, whereas possible indicators of existing disorders are detectable in serum.

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“…Therefore, design and interpretation of clinical studies in asthma and the use of FENO in routine clinical practice depends greatly on the reproducibility and the safety of FENO measurements. Reproducibility of FENO measurements was studied by several groups, but either the statistical analysis was inappropriate (correlation coefficient) [12], or exhalation flow rate was either not registered [13], or was different from the American Thoracic Society (ATS) recommendations [14].Because of uncertainty regarding the reproducibility and the safety of standardised FENO measurements made in accordance with the ATS recommendations [5], these issues were examined in asthmatic and healthy subjects, including both adults and children. …”

mentioning

confidence: 99%

Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children

et al. 2003

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Airway inflammation in asthma is not measured routinely in clinical practice. Fractional exhaled nitric oxide (FENO), a marker of airway inflammation, is increasingly used as an outcome measure in asthma intervention studies and yet the reproducibility of FENO measurements is unknown.The reproducibility, day-to-day, diurnal variation and perception of standardised FENO measurements were examined in 59 subjects (40 children aged 7-13 yrs and 19 adults aged 18-60 yrs), both healthy (n=30) and with mild (n=29) asthma. FENO was measured on five consecutive days (four measurements on the same day) for adults and twice on the same day for children.The coefficient of reproducibility expressed as the mean pooled standard deviation (n=59, 675 estimations) was 2.11 parts per billion (ppb) and intraclass correlation coefficient was 0.99 in both children and adults. FENO was significantly higher in asthma subjects (32.3 ppb) than in healthy subjects (16.3 ppb). There was no diurnal or day-to-day variation, or a learning effect, as the result of FENO measurements were identical at results of the beginning and at the end of the study.It was concluded that fractional exhaled nitric oxide measurements are simple, reproducible, free from diurnal and day-to-day variation, and acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician. Asthma is an inflammatory disease, yet airway inflammation is not measured directly and routinely in clinical practice [1]. This makes management of asthma difficult, because it is based on indirect measurements of airway inflammation, such as symptoms and lung function. Symptoms may not accurately reflect the extent of underlying inflammation due to differences in perception, and lung function tests may have little room for improvement in mild asthma. None of these parameters is able to distinguish the effect of different doses of inhaled corticosteroids and both may be affected by bronchodilators. The latter is particularly important because of a recent trend towards use of lower doses of inhaled corticosteroids in combination with long-acting b 2 -agonists.Current invasive (bronchoscopy), or semi-invasive (sputum induction) direct methods to measure airway inflammation are difficult to use repeatedly in clinical practice. The use of sputum induction is limited by its pro-inflammatory effect [2], and a considerable bronchospasm has been reported during sputum induction in moderate (14%) and severe (25%) asthma, as a result of the procedure [3].There has been an explosion of research into exhaled nitric oxide (NO) since levels were found to be increased in asthma [1,4]. Standardised [5,6] measurements of fractional exhaled NO (FENO) provide a completely noninvasive means of monitoring airway inflammation and anti-inflammatory treatment in asthma [1], including a dose-dependent onset and duration of action of inhaled corticosteroids [7]. It may be useful in patients using fixed combination inhalers (corticosteroids and longacting b 2 -agon...

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Reproducibility of measurements of exhaled NO, and cell count and cytokine concentrations in induced sputum

Cited by 34 publications

References 20 publications

Sputum induction

Sputum induction

Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders

Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children

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