Non‐invasive assessment of bronchial inflammation in asthma: no correlation between eosinophilia of induced sputum and bronchial responsiveness to inhaled hypertonic saline

Iredale, M. J.; Wanklyn, S. A. R.; Phillips, I. P.; Krausz, T; Ind, Philip W.

doi:10.1111/j.1365-2222.1994.tb02725.x

Cited by 106 publications

(70 citation statements)

References 22 publications

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“…In addition, eosinophils in sputum are associated with bronchial hyperresponsiveness (BHR) when measured by methacholine [14] or histamine [15], but not by hypertonic saline [16]. Moreover, it has been shown in subjects with asthma that eosinophil numbers in sputum reflect those in bronchial washings, bronchoalveolar lavage fluid, and bronchial biopsies [17,18].…”

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confidence: 99%

Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity

Grootendorst¹,

Bos²,

Romeijn³

et al. 1999

Eur Respir J

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This study examined the safety of sputum induction and the relation between sputum cell counts and clinical parameters in adolescents with severe persistent asthma.Within 5 days, induced sputum and reversibility in forced expiratory volume in one second (FEV1), quality of life, provocative concentration causing a 20% fall in FEV1 (PC20) of adenosine monophosphate and histamine, exercise-induced bronchoconstriction, overall asthma severity index, and blood eosinophils were collected in 20 atopic adolescents with moderate-to-severe persistent asthma (12±18 yrs of age, FEV1 65±110% of predicted, on 500±2,000 mg inhaled steroids daily).FEV1 was reversible by 13.32.3% pred. After sputum induction, FEV1 was still increased by 9.02.6% pred as compared to the pre-salbutamol baseline. Sputum contained, median (range): 12.4 (0.4±59.5)% squamous cells, 47.3 (6.8±84.0)% macrophages, 39.0 (4.6±84.8)% neutrophils, 4.8 (1.0±12.4)% lymphocytes, 0.4 (0±10.8)% eosinophils and 3.6 (0±23.4)% bronchial epithelial cells. Sputum eosinophils showed a trend towards a significant association with the overall asthma severity index (r=0.46, p=0.06) and correlated inversely with baseline FEV1 (r=-0.51, p=0.03).In conclusion, sputum can be induced safely in adolescents with moderate-to-severe persistent asthma, if pretreated with b 2 -agonists. Despite relatively low sputum eosinophil counts in these patients on inhaled steroids, the association of eosinophil numbers with baseline forced expiratory volume in one second and asthma severity index favours a role of induced sputum in monitoring adolescents with severe asthma. Eur Respir J 1999; 13: 647±653.

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confidence: 99%

Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity

Grootendorst¹,

Bos²,

Romeijn³

et al. 1999

Eur Respir J

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“…[12][13][14][15] In many studies, however, the level of significance of the interrelations among all these outcome measures has been found to be clinically irrelevant. [16][17][18][19][20] In this regard we have recently found that sputum measurements of eosinophilic inflammation do not accurately reflect current clinical indices of asthma severity in patients with chronic, stable asthma 12 and might therefore provide complementary data for monitoring of the disease.…”

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confidence: 99%

Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: Results of a factor analysis

Rosi

Ronchi

Grazzini

et al. 1999

Journal of Allergy and Clinical Immunology

148

111

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Background: Recent studies have shown weak associations among FEV 1 , bronchial hyperresponsiveness (BHR), sputum eosinophils, and sputum eosinophil cationic protein (ECP), suggesting that they are nonoverlapping quantities. The statistical method of factor analysis enables reduction of many parameters that characterize the disease to a few independent factors, with each factor grouping associated parameters. Objective: The purpose of this study was to demonstrate, by using factor analysis, that reversible airway obstruction, BHR, and eosinophilic inflammation of the bronchial tree, as assessed by cytologic and biochemical analysis of sputum, may be considered separate dimensions that characterize chronic bronchial asthma. Methods: Ninety-nine clinically stable patients with a previous diagnosis of asthma underwent spirometry, sputum induction, and histamine inhalation tests. Results: Most patients were nonobstructed (FEV 1 , 91% ± 20%); a low level of bronchial reversibility (FEV 1 increase after β 2 -agonist, 7.8% ± 9.2%) and BHR (histamine PC 20 FEV 1 geometric mean, 0.98 mg/mL) were found. Sputum eosinophil differential count (12.4% ± 17.7%) and sputum ECP (1305 ± 3072 µg/mL) were in the normal range of our laboratory in 38 and 22 patients, respectively. Factor analysis selected 3 different factors, explaining 74.8% of variability. Measurements of airway function and age loaded on factor I, PC 20 FEV 1 and β 2 -response loaded on factor II, and sputum ECP and eosinophils loaded on factor III. Additional post hoc factor analyses provided similar results when the sample was divided into 2 subgroups by randomization, presence of airway obstruction, degree of BHR, percentage of sputum eosinophils, or concentration of sputum ECP. Conclusions: We conclude that airway function, baseline BHR, and airway inflammation may be considered separate dimensions in the description of chronic asthma. Such evidence supports the utility of routine measurement of all these dimensions. (J Allergy Clin Immunol 1999;103:232-7.)

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“…Examination of spontaneous or induced sputum promises to be a reliable direct method by which this can be achieved noninvasively [2][3][4][5][6][7][8].…”

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confidence: 99%

Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination

Pizzichini

Pizzichini²,

Efthimiadis³

et al. 1996

Eur Respir J

263

212

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Sputum examination is being used increasingly as a noninvasive method to assess airway inflammation. Expectorated sputum has variable contamination with saliva. Methods of processing have included the selection of portions of the sample considered to be representative of pulmonary origin versus use of the whole specimen, which is confounded by varying volumes of saliva. We compared cell profiles and eosinophilic cationic protein (ECP) concentration in sputum selected from the expectorate and in the usually discarded residual portion to determine to what degree salivary contamination is minimized and if the results are representative of lower respiratory secretions. Sputum was induced with hypertonic saline in six healthy and nine asthmatic subjects. All portions considered to be of pure lower respiratory tract origin were selected from the residual. The selected and residual portions were treated with dithiothreitol, total cell counts and cell viability were obtained, cytospins were made for differential cell counts and supernatant was collected for ECP assay. Selected portions of the specimens, in comparison with the residual portion showed: little squamous cell contamination (median 1.2 vs 70%; p < 0.001); higher total cell counts.mL-1 (5.1 vs 0.5 x 10(6) cells.mL-1; p < 0.001); higher number of viable nonsquamous cells per sample (1.9 vs 0.6 x 10(6) cells; p < 0.001); higher slide quality score (7 vs 4; p < 0.001); and higher levels of ECP (768 vs 136 micrograms.L-1; p < 0.001). There were no differences in the differential cell counts of eosinophils (1.3 vs 3.8%), neutrophils (44 vs 32%), and lymphocytes (0.6 vs 0.6%). While the proportion of macrophages was lower (36 vs 54%; p < 0.05), the absolute number (41 vs 19 x 10(4) cells; p < 0.05) was higher in the selected portion. In summary, selection of all portions of induced sputum from the expectorate minimized the confounding influence of saliva. Loss of nonsquamous cells in the residual portion was variable but usually less than one third of those in the selected portion. With one exception, this loss had little influence on the differential counts of inflammatory cells. Similar observations apply to eosinophilic cationic protein levels. We conclude that, in healthy subjects and treated asthmatics, inflammatory markers in the selected portion of the expectorate can be used to represent those in the lower respiratory tract in general.

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Non‐invasive assessment of bronchial inflammation in asthma: no correlation between eosinophilia of induced sputum and bronchial responsiveness to inhaled hypertonic saline

Cited by 106 publications

References 22 publications

Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity

Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity

Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: Results of a factor analysis

Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination

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