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Sputum induction for the diagnosis of pulmonary disease in HIV positive patients.

We prospectively compared sputum induction with bronchoalveolar lavage (BAL) in HIV positive patients presenting with acute respiratory episodes and also assessed the effects of using an experienced respiratory physiotherapist on the diagnostic yield from induced sputum. One hundred and fifty-one consecutive patients underwent sputum induction, in 96 the procedure was supervised by nursing and medical staff with no specific expertise (group I); in 55 patients a physiotherapist supervised sputum induction (group 2). Nine patients refused BAL having undergone sputum induction. Of the remaining 142 patients sputum induction failed (no sample expectorated) in 28 patients (25 from group 1 and three from group 2), the sample was inadequate (the material expectorated was not from the lower respiratory tract) in 29, and was adequate in 85 patients. Pneumocystis carinii was diagnosed in 82 patients (51 from group 1 and 31 from group 2). The sensitivity of induced sputum for the diagnosis of P. carinii was 13% and of BAL was 77%. In the subgroup of patients with an adequate induced sputum sample, the sensitivity of induced sputum was 28% and of BAL was 73%. Of the remaining 60 patients, 27 had other diagnoses made by induced sputum and BAL (eight patients), BAL only (15 patients) and induced sputum only (four patients). Eleven patients had bronchitis and responded to oral antibiotics. In 22 patients induced sputum and BAL were negative; alternative diagnoses were established by lung biopsy or by culture of blood, urine or CSF. During sputum induction, 15 patients had nausea and vomiting, eight became dyspnoeic, three had intractable cough and one developed acute bronchoconstriction; 17 patients found the procedure unpleasant. Compared with BAL, induced sputum has a lower diagnostic yield for P. carinii and other pathogens. Use of experienced, dedicated personnel increases the number of successful attempts at sputum induction but does not increase the diagnostic yield. Fibreoptic bronchoscopy and bronchoalveolar lavage remain necessary for patients with negative results from induced sputum and those whose disease course is at variance with the diagnosis made by sputum induction.

Acquired Immunodeficiency Syndrome↗

Comparison of spontaneous and induced sputum for investigation of airway inflammation in chronic obstructive pulmonary disease.

BACKGROUND: Although sputum induction is used as a technique to investigate lower airway inflammation in asthmatic subjects, advantages over spontaneous sputum in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. METHODS: Samples of spontaneous sputum and sputum induced with 3% hypertonic saline for 14 minutes were collected from 27 patients with chronic obstructive pulmonary disease (COPD) who usually produced spontaneous sputum. Spirometric indices and oxygen saturation (Sao2) were measured at seven minute intervals. The spontaneous, seven and 14 minute sputum samples were analysed for total and differential cell counts, cell viability, and interleukin 8 levels. RESULTS: Analysis of the sputum revealed that median cell viability was higher in the seven minute (62.8%; p = 0.004) and 14 minute (65%; p = 0.001) induced sputum samples than in spontaneous sputum (41.2%). There was no significant difference in total and differential cell counts or in interleukin 8 levels between spontaneous and induced sputum. During the sputum induction procedure the mean (SD) fall in forced expiratory volume in one second (FEV1) was 0.098 (0.111) 1 (p < 0.001) and in forced vital capacity (FVC) was 0.247 (0.233) 1 (p < 0.001). There was a small but significant fall in Sao2 during sputum induction (p = 0.03). CONCLUSIONS: Induced sputum contains a higher proportion of viable cells than spontaneous sputum. There are no significant differences between the sputum samples obtained at seven minutes and at 14 minutes of hypertonic saline nebulisation. Sputum induction is safe and well tolerated in patients with COPD.

Aged↗

The tolerability, safety, and success of sputum induction and combined hypertonic saline challenge in children.

Induced sputum using hypertonic saline (HS) is a useful research tool to study airway inflammation (AI). HS provocation testing can also be used to measure airway hyperresponsiveness (AHR). A combined HS challenge and sputum induction procedure has been developed to permit assessment of AI and AHR in a single test. The aim of this study is to report the success and tolerability of sputum induction alone, and in combination with a HS bronchial provocation challenge. Sputum induction alone was performed with beta2-agonist pretreatment. In the combined challenge, no beta2-agonist pretreatment was used. A high-output ultrasonic nebulizer with valve box and tubing were used to deliver 4.5% saline in doubling time periods from 0.5 s to 4 min. Outcomes assessed were completion of the test protocol, adequacy of sputum samples, decrease in FEV1, and adverse effects during the procedure. Fifty-three children who underwent a sputum induction alone, and 182 children who underwent a combined sputum induction and bronchial provocation using HS. Sputum induction alone was well tolerated, with 98% of children completing the procedure and only 4% experiencing a significant (> 15%) fall in FEV1. An adequate sample of sputum was obtained in 92% of children. The combined challenge was completed by 90% of children. A distressing cough occurred in 13% of children and irritation of the mucosa in 1% of children. In the combined challenge an adequate sample of sputum was obtained in significantly fewer children than with sputum induction alone (70% versus 92%, p < 0.05). Sputum cellular changes reflected the shorter nebulization time with sputum induction alone. We conclude that induction of sputum using HS after pretreatment with bronchodilator is well tolerated with a high success rate in children. Combining the HS challenge with sputum induction provides additional information and is a useful means of comparing AHR and AI simultaneously, but at the expense of having a reduced success rate in obtaining an adequate sample of sputum, as well as increased side effects.

Adolescent↗

Induced sputum in the diagnosis of peripheral lung cancer not visible endoscopically.

The diagnosis of small peripheral lung cancer is difficult to achieve by non-invasive methods. We hypothesized that in these patients induced sputum might ncrease the diagnostic yield over spontaneous sputum, representing a good diagnostic alternative in selected patients. We prospectively evaluated 60 patients with peripheral lung lesions and normal bronchoscopic evaluation. Six samples of sputum (three spontaneous and three induced with nebulization of hypertonic saline) before bronchoscopy and six samples of sputum after bronchoscopy (three spontaneous and three induced) were obtained in each subject. Forty-two out of the 60 patients included were finally diagnosed with lung cancer. Eighteen patients were diagnosed with different benign conditions of the lung. Overall, malignant cells in sputum were observed in 21 patients and in all but one, the final diagnosis of lung cancer was achieved. Only one patient with a pseudoinflammatory tumour of the lung had a false-positive result in one spontaneous sputum sample. The diagnosis of lung cancer was obtained in 18 patients with the induced sputum (43%) and in 14 patients with spontaneous sputum (31%) (P=NS). Samples of induced sputum were more adequate for cytological analysis than samples of spontaneous sputum (P < 0.001). Of 13 patients with peripheral lung neoplasms of 2 cm or less in diameter, five were diagnosed using induced sputum (38%) and only one using spontaneous sputum (8%) (P<0.05). In conclusion, induced sputum is a valuable technique for the diagnosis of peripheral lung cancer. Induced sputum gives better quality specimens and better diagnostic yield in small lesions than the spontaneous sputum and may be indicated in selected patients with disseminated disease, inoperability or severe co-morbities.

Adenocarcinoma↗

Screening tuberculosis suspects using two sputum smears.

SETTING: Ntcheu district hospital, Malawi. OBJECTIVE: To assess a screening strategy for tuberculosis (TB) suspects using two sputum smears. DESIGN: A strategy of screening all TB suspects with two sputum smears for 6 months (1 July-31 December 1998) was compared with the period 1 January to 30 June 1998 during which the strategy of screening TB suspects with three sputum smears was in use. All chest radiographs of patients with negative sputum smears were assessed, and in those with pulmonary cavities and extensive disease a third sputum smear was examined. Data were collected from the laboratory sputum register and the TB register. The two 6-month periods were compared. RESULTS: In the laboratory register, using a two-sputum strategy, 186 (16%) of 1152 TB suspects were smear-positive, a result that was no different than when the three-sputum strategy was used, where 173 (16%) of 1106 TB suspects were smear-positive. The clinical pattern of TB using the different screening strategies was similar, with 58% of registered patients smear-positive with the two-sputum strategy and 54% smear-positive with the three-sputum strategy. In the first 6 months 3177 sputum smears were examined compared to 2266 smears in the second 6 months, a 29% reduction in the number of smears examined. The cost of consumables using the strategy of three sputum smears was USD $731 compared with USD $521 using the strategy of two sputum smears. C O N C L U S I O N S: Screening TB suspects using two sputum smears is as effective as screening using three sputum smears, and is associated with less laboratory work and savings in costs.

Cost Control↗

IL-2 and IL-10 levels in induced sputum and serum samples of asthmatics.

BACKGROUND: There is consisting evidence that asthma is associated with airway inflammation. Originally IL-10 and IL-2 were described as lymphokines produced by T cells in mediating cellular infiltration into the airways and continue to be of interest in evaluating asthma pathogenesis. The aim of this study was to evaluate the serum and sputum levels of IL-2 and IL-10 in asthmatic subjects and healthy controls and to correlate disease activity and other clinical indices with concentrations of IL-2 and IL-10 in serum and sputum samples. METHODS: We evaluated cell profiles and IL-2 and IL-10 levels in induced sputum samples and in serum samples of 6 mild, 5 moderate, 7 severe asthmatic patients and 5 healthy controls by using ELISA. RESULTS: The mean IL-2 in sputum samples of asthmatics and controls were 35.3 +/- 13.2 pg/ml and 35.3 +/- 8.4 pg/ml, respectively. The mean IL-2 in serum samples of asthmatics and controls were 42.7 +/- 21.1 pg/ml and 30.3 +/- 2.4 pg/ml, respectively. Both levels did not result in any statistically significant difference between asthmatics and controls. There was no correlation between serum and sputum IL-2 levels, however sputum IL-2 levels correlated with percentage of sputum lymphocytes (p < 0.03, r = 0.51). The mean IL-10 levels in sputum samples of asthmatics and controls were 4.4 +/- 3.3 pg/ml and 3.9 +/- 5.9 pg/ml, respectively, the mean IL-10 level in serum of asthmatics and controls were 4.1 +/- 3.8 pg/ml and 2.3 +/- 2.5 pg/ml, respectively. We could not find statistically significant difference of serum or sputum IL-10 levels between asthmatics and controls. There was only correlation between serum and sputum IL-10 levels in asthmatics (p < 0.0008, r = 0.73). There was no difference between asthmatic subgroups regarding sputum and serum levels of IL-2 and IL-10. No correlation could be demonstrated between sputum or serum IL-2 and IL-10 levels and clinical severity. CONCLUSIONS: We have demonstrated the presence of detectable concentrations of the IL-2 and IL-10 in serums and induced sputum samples of asthmatics, however, they have no predictive value for asthma since their levels are not increased in asthmatic patients over controls. Moreover, IL-2 level positively correlated with lymphocyte percentage in induced sputum. The results suggest that measurement of IL-2 and IL-10 concentrations in serum and sputum will not be of diagnostic use in asthma and a reflection of the severity of asthmatic airway inflammation.

Adult↗

A novel method of sputum processing for cytologic diagnosis of lung cancer.

OBJECTIVE: To compare the diagnostic sensitivity and cytologic findings of the sputum-processing method with those of the traditional sputum smear method. STUDY DESIGN: From May to December 2001, 300 consecutive sputum samples were collected from 168 patients suspected of having lung cancer in the Chest Department, Taipei Veterans General Hospital. After the sputum smear method, the remaining sputum material was processed by homogenization, filtration and fixation. All the slides were stained with Papanicolaou stain and reviewed by 2 cytologists. RESULTS: Of the 300 sputum samples, 141 from 79 patients were finally diagnosed as lung malignancies. The mean number of sputum samples was 1.78 per patient. Among the 79 patients, 46 had peripheral lung malignancies (58.2%). The overall diagnostic sensitivities of sputum smear and sputum-processing methods were 29% and 31%, respectively (P = .776). Tumor location and cell types did not change the difference significantly; however, among patients with small cell lung cancer, there was a higher detection rate with the sputum-processing method (50% vs. 20%, P = .350). Eight patients with negative results with the sputum smear had positive results with the sputum-processing method (8 of 79 = 10.1%). Microscopic morphologic differences between the 2 methods were described. CONCLUSION: There was no significant difference in diagnostic sensitivity between the sputum smear and sputum-processing methods. However, the sputum-processing method may play a role in patients with small cell lung carcinoma.

Diagnostic Tests, Routine↗

Eosinophil count and eosinophil cationic protein concentration of induced sputum in the diagnosis and assessment of airway inflammation in bronchial asthma.

Measurement of eosinophil percentages and ECP concentration in induced sputum may be useful in the diagnosis and assessment of the variability of airway inflammation in bronchial asthma (BA). To evaluate the usefulness of sputum eosinophil counts and ECP concentrations in the diagnosis of BA, we measured these parameters in 68 patients with respiratory complaints. In addition, we followed-up 14 BA patients with variable airflow limitation for 45.4 +/- 10.4 days. The BA group (n = 41) showed a higher percentage of sputum eosinophilia (24.5 +/- 7.6 vs. 2.2 +/- 2.9%, p < 0.001) and a higher level of sputum ECP (198.2 vs. 90.6 micrograms/L, p < 0.05) than those in the nonasthmatic group (NBA, n = 27). The sensitivity and specificity of sputum eosinophilia (> or = 5%) for the diagnosis of BA were 85.4% and 92.6%, respectively, which were better than the sensitivity (68.3%) and specificity (55.5%) of the increased level of sputum ECP (> or = 100 micrograms/L). Patients with moderate-to-severe persistent BA had a higher percentage of sputum eosinophil (n = 23, 34.6 +/- 10.6%) than those of mild persistent BA (n = 18, 10.7 +/- 5.2%, p < 0.01), but we could not find significant difference in ECP levels between mild persistent and moderate-to-severe persistent asthma. The percentages of sputum eosinophilia showed a moderate correlation with ECP (r = 0.4358, p < 0.01) and with the peak expiratory flow rate (PFR, r = -0.4746, p < 0.01) but sputum ECP did not correlate with PFR. In 14 BA patients who were followed, there was a relationship between changes of PFR and the percentage of sputum eosinophil (r = -0.7238, p < 0.01), but the change of PFR did not correlate with the change of sputum ECP levels. These results suggest that the sputum eosinophil count and sputum ECP level could be helpful in the diagnosis of BA, but that sputum ECP is not satisfactory for the assessment of variability of airway eosinophilic inflammation during the initial anti-inflammatory management of BA.

Adult↗

Analysis of sputum cell counts during spontaneous moderate exacerbations of asthma in comparison to the stable phase.

BACKGROUND: Acute airway inflammation is considered to characterize asthma exacerbations, but its specific cellular pattern has not yet been completely evaluated. AIM: To evaluate the prevalence of sputum eosinophilia during acute asthma exacerbations of moderate severity, compared with a stable phase of the disease, and to assess the concordance between changes in pulmonary function and sputum eosinophilia in the period between exacerbation and post exacerbation. METHODS: We compared sputum and blood inflammatory cell counts in 29 asthmatic subjects during a spontaneous moderate exacerbation of asthma (visit 1) with sputum and blood cell counts measured 4 weeks after the resolution of asthma exacerbation (visit 2). At visit 1, all subjects required an appropriate 1 week treatment with oral corticosteroids. RESULTS: At visit 1, all subjects were able to collect spontaneous sputum, whereas at visit 2 sputum was induced by inhalation of hypertonic saline (NaCl 3, 4, and 5%, 10 minutes each) with beta2-agonist pretreatment. Asthma exacerbation was accompanied by a significant increase in sputum eosinophil percentages compared with levels after exacerbation [25% (1-78) versus 4% (0-23), p<0.05). Only four subjects showed low sputum eosinophil percentages during exacerbation, and these showed no differences in main clinical findings with respect to subjects with sputum eosinophilia. At visit 2, the stability of asthma was assessed on the basis of PEF, FEV1, symptoms, and use of rescue beta2-agonist. Asthma was defined as stable in 21 out of 29 subjects. Sputum eosinophil percentages fell significantly between visit 1 and visit 2 in both stable and unstable patients, but at visit 2 sputum eosinophil percentages were still high in subjects with unstable asthma. In patients who proved to be stable at visit 2, there was a significant correlation between the changes recorded in sputum eosinophil percentages and in FEV1 between the two visits (rho: 0.723, p<0.001). CONCLUSION: Sputum cosinophil but not neutrophil percentages increase in most asthmatic subjects during moderate exacerbation of asthma. Changes in the degree of airway eosinophilic inflammation are related to changes in the severity of airway obstruction during asthma exacerbation.

Asthma↗

Macromolecular mechanisms of sputum inhibition of tobramycin activity.

Tobramycin, an aminoglycoside antibiotic, is used in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis patients. Tobramycin bioactivity, however, is antagonized by sputum. Glycoproteins (mucins) and high-molecular-weight DNA make up 2 to 3% (P. L. Masson and J. F. Heremans, p. 412-475, In M. J. Dulfano, ed., Sputum: Fundamentals and Clinical Pathology, 1973) and 3 to 10% (W. S. Chernick and G. J. Barbero, Pediatrics 24:739-745, 1959, and R. Picot, I. Das, and L. Reid, Thorax 33:235-242, 1978) of the dry weight of sputum, respectively. tobramycin binds to both mucins and DNA obtained from sputum (R. Ramphal, M. Lhermitte, M. Filliat, and P. Roussel, J. Antimicrob. Chemother. 22:483-490, 1988). In vitro, recombinant human DNase (rhDNase) hydrolyzes high-molecular-weight DNA of > 50 kb within sputum to fragments of 2 to 4 kb. Studying dialyzable tobramycin, we examined drug binding to whole sputum and to "mock sputum," which consisted of porcine gastric mucin and calf thymus DNA. We also studied the effects of rhDNase treatments of sputum, mock sputum, and calf thymus DNA on tobramycin binding. We found that treatments of sputum, mock sputum, and calf thymus DNA with rhDNase did not significantly increase the tobramycin bioactivity within the dialysates; surprisingly, sputum binding of tobramycin was increased by rhDNase. We conclude that rhDNase does not increase the bioactivity of tobramycin in sputum.

Adult↗

Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis.

BACKGROUND: Previous studies suggest that bronchoscopy and a single induced sputum sample are equally effective for diagnosing pulmonary tuberculosis. METHODS: In a prospective study of subjects with possibly active pulmonary tuberculosis, the diagnostic yield of three induced sputum tests was compared with that of bronchoscopy. Subjects either produced no sputum or (acid fast) smear negative sputum. Bronchoscopy was only performed if at least two induced sputum samples were smear negative. RESULTS: Of 129 subjects who completed all tests, 27 (21%) had smear negative and culture positive specimens, 14 (52%) on bronchoscopy and 26 (96%) on induced sputum (p<0.005). One patient was culture positive on bronchoscopy alone compared with 13 on induced sputum alone; 13 were culture positive on both tests. Induced sputum positivity was strikingly more prevalent when chest radiographic appearances showed any features of active tuberculosis (20/63, 32%) than when appearances suggested inactivity (1/44, 2%; p<0.005). Induced sputum costs were about one third those of bronchoscopy, and the ratio of costs of the two tests per case of tuberculosis diagnosed could be as much as 1:6. CONCLUSIONS: In subjects investigated for possibly active or inactive tuberculosis who produce no sputum or have smear negative sputum, the most cost effective strategy is to perform three induced sputum tests without bronchoscopy. Induced sputum testing carries a high risk of nosocomial tuberculosis unless performed in respiratory isolation conditions. The cost benefits shown could be lost if risk management measures are not observed.

Adolescent↗