Analysis of Induced Sputum after Air and Ozone Exposures in Healthy Subjects

Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis.A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre-and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8.There were significant (p<0.05) pre-to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post-minus pre-exposure value for these variables.The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables. Eur Respir J 2000; 15: 856±862.

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 77%

Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release

Criqui¹,

Solomon²,

Welch³

et al. 2000

“…Analysis of induced sputum results has shown them to correlate well with data obtained from bronchial wash and bronchoalveolar lavage [24,25]. In air pollution research, induced sputum has previously proved valuable in the evaluation of the airway effects of ozone [26] and nitrogen dioxide [27].…”

mentioning

confidence: 99%

Airway inflammation following exposure to diesel exhaust: a study of time kinetics using induced sputum

Nordenhäll¹,

Pourazar²,

Blomberg³

et al. 2000

129

The adverse health effects of particulate matter pollution are of increasing concern. In a recent bronchoscopic study in healthy volunteers, pronounced airway inflammation was detected following exposure to diesel exhaust (DE). The present study was conducted in order to evaluate the time kinetics of the inflammatory response following exposure to DE using induced sputum from healthy volunteers.Fifteen healthy nonsmoking volunteers were exposed to DE particles with a 50% cut-off aerodynamic diameter of 10 mm 300 mg . m -3 and air for 1 h on two separate occasions. Sputum induction with hypertonic saline was performed 6 and 24 h after each exposure. Analyses of sputum differential cell counts and soluble protein concentrations were performed.Six hours after exposure to DE, a significant increase was found in the percentage of sputum neutrophils (37.7 versus 26.2% p=0.002) together with increases in the concentrations of interleukin-6 (12.0 versus 6.3 pg . mL -1 , p=0.006) and methylhistamine (0.11 versus 0.12 mg . L -1 , p=0.024). Irrespective of exposure, a significant increase was found in the percentage of sputum neutrophils at 24 as compared to 6 h, indicating that the procedure of sputum induction itself may change the composition of sputum.This study demonstrates that exposure to diesel exhaust induces inflammatory response in healthy human airways, represented by an early increase in interleukin -6 and methylhistamine concentration and the percentage of neutrophils. Induced sputum provides a safe tool for the investigation of the inflammatory effects of diesel exhaust, but care must be taken when interpreting results from repeated sputum inductions. Eur Respir J 2000; 15: 1046±1051. The adverse health effects of particulate matter (PM) pollution are of increasing concern as several epidemiological studies have revealed an association between elevations in ground level PM concentrations and increased morbidity and mortality from cardiovascular and respiratory causes [1±7].Recently, attention has been directed towards the particulate air pollution emitted from diesel engines. The number of diesel-powered cars is rising and diesel engines emit up to 100 times more particles than petrol engines [8,9]. Diesel exhaust (DE) particles contain a carbonaceous core, which adsorbs various metals and organic compounds on its surface. Consequently, the biological effects of DE may be explained by not only the gases and pure particles but also by these surface components.The number of studies investigating the effects of DE has increased during recent years. In working environments, exposure to DE has been associated with various symptoms related to the eyes and airways [10±12]. In experimental chamber studies, DE has been shown to cause airway symptoms [13] and to induce an acute inflammatory response in human airways as reflected in bronchoalveolar lavage [14,15] and bronchial biopsy [16] samples. Further, local nasal challenge with DE particles has been reported to enhance immunoglobulin E production in the ...

“…However, the symptoms of asthma are not specific, many patients appreciate variable airflow limitation poorly [6] and these features do not necessarily correlate with airway eosinophilia [7]. Furthermore, there are other types of inflammation, particularly neutrophilic, caused by bacterial [8] and viral infections [9] or pollutants [10], which may not respond to treatment with corticosteroids. It is therefore not unreasonable to consider that the indirect clinical assessment of airway inflammation may often be inaccurate.…”

mentioning

confidence: 99%

Clinical judgement of airway inflammation versus sputum cell counts in patients with asthma

Parameswaran

Pizzichini

et al. 2000

The inflammatory component of asthma is usually assessed indirectly by symptoms and spirometry, these may be inaccurate. It can now be assessed directly and reliably by the examination of sputum cell counts. There is no information on how clinical assessment of the presence and type of airway inflammation compares with actual measurements.In this single-centre observational study, sputum was collected from 76 consecutive adults with asthma attending a tertiary chest clinic after their physicians had recorded the expected cell counts in sputum. The authors examined the extent of agreement between clinical judgement of sputum cell counts and actual counts in asthmatic patients (Cohen's Kappa) and the possible predictors of agreement (multiple logistic regression).Sixty-seven of the 76 sputum samples were suitable for analysis. Agreement between expected and actual cell counts occurred in 30/67 patients. The overall agreement for the different cell types was poor (estimated k=0.14, 95% confidence interval (CI)=0.02, 0.26). The experience of the physician in using sputum cell counts in clinical practice, steroid requirement at the time of assessment, and control of asthma as assessed by the physician or by the patient could not predict the chances of agreement or disagreement. Unaware of the sputum results, the physicians often changed treatment in a way that seemed inappropriate for the cell counts present.There is poor agreement between clinical judgement of the presence and type of airway inflammation in asthmatic patients and sputum cell counts. The impact of sputum examination on the outcomes of anti-inflammatory treatment now needs investigation. Eur Respir J 2000; 15: 486±490.