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A two-stage logistic model based on the measurement of pro-inflammatory cytokines in bronchial secretions for assessing bacterial, viral, and non-infectious origin of COPD exacerbations.
COPD 2005; 2(1):7-16COPD

Abstract

Exacerbations often complicate the progressive course of chronic obstructive pulmonary disease (COPD), mainly due to infectious agents. The precise role of bacterial infections in the course and the pathogenesis of COPD has been a source of controversy for decades. Also viruses and other non-infectious causes of exacerbation play a relevant role and also contribute to persisting airway inflammation. Usually, the etiologic identification of the infective causes of COPD require considerable time and costs. The development of more rapid, reliable, and widely applicable methods to promptly define the etiology of COPD exacerbations should represent a relevant issue in devising earlier and more specific strategies for their effective therapeutic control.

AIM

Of the study was to assess the predictive role of some pro-inflammatory cytokines measured in spontaneous bronchial secretions in discriminating the main infectious causes of COPD exacerbations.

METHODS

124 subjects with moderate COPD (51-79 y; mean basal FEV1 = 49.6% pred. +/- 4.6 sd; FEV1 reversibility +3.9% from baseline +/- 4.8 sd after salbutamol 200 mcg) were studied during acute exacerbation. Respiratory viruses were isolated from bronchial secretions in 21 cases; common bacteria (CFU > or = 10(6)/ml) in 28 cases; Pseudomonas Aeruginosa (Ps.Ae.; CFU > or = 10(6)/ml) in 20 cases. The cytokines IL1beta, IL8, and TNFalpha (pg/ml; Immulite; Diagnostic Product Corp, Los Angeles, CA, USA), and neutrophils (% total count) were measured in bronchial secretions of all patients.

STATISTICS

A two-stage logistic model was chosen for discriminating the different causes of COPD exacerbations (such as: non-infectious, or viral, bacterial, or due to Ps.Ae.).

RESULTS

At the first decisional step, the two-stage logistic model proved that TNFalpha levels in bronchial secretions recognise clearly patients belonging to the Ps.Ae. group from those of all other groups (Area under ROC curve = 0.96; 95% CI = 0.91-0.99), and that, at the second decisional step, IL8 + IL10 levels discriminate patients with bacterial causes (such as all bacteria) from the non-infected ones and from those with a viral cause of exacerbation (Area under ROC curve = 0.87; 95% CI = 0.77-0.94). Neutrophil percent count did not support any contribution in discriminating the different subgroups of COPD subjects.

CONCLUSIONS

When exacerbated, COPD subjects express different patterns of pro-inflammatory mediators in bronchial secretions, which appear modulated according to the etiological cause of the exacerbation. In particular, TNFalpha concentration per se enables recognition of COPD exacerbations due to Ps.Ae., while IL8 + IL1beta levels prove helpful in discriminating those to common bacteria from those to viral agents and to non-infectious causes. When present data are further confirmed, the use of a decisional rule based on cytokine measurements might be regarded as a helpful predictive tool. As measures of pro-inflammatory cytokines are low-cost, simple, and faster to perform, they could support rapid clinical decision making at the bedside regarding therapeutic strategy for COPD exacerbations, in particular when they are needed for severe COPD patients.

Authors+Show Affiliations

Lung Department, "Orlandi" General Hospital, Bussolengo, Verona, Italy. rdalnegro@ulss22.ven.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17136956

Citation

Dal Negro, Roberto W., et al. "A Two-stage Logistic Model Based On the Measurement of Pro-inflammatory Cytokines in Bronchial Secretions for Assessing Bacterial, Viral, and Non-infectious Origin of COPD Exacerbations." COPD, vol. 2, no. 1, 2005, pp. 7-16.
Dal Negro RW, Micheletto C, Tognella S, et al. A two-stage logistic model based on the measurement of pro-inflammatory cytokines in bronchial secretions for assessing bacterial, viral, and non-infectious origin of COPD exacerbations. COPD. 2005;2(1):7-16.
Dal Negro, R. W., Micheletto, C., Tognella, S., Visconti, M., Guerriero, M., & Sandri, M. F. (2005). A two-stage logistic model based on the measurement of pro-inflammatory cytokines in bronchial secretions for assessing bacterial, viral, and non-infectious origin of COPD exacerbations. COPD, 2(1), pp. 7-16.
Dal Negro RW, et al. A Two-stage Logistic Model Based On the Measurement of Pro-inflammatory Cytokines in Bronchial Secretions for Assessing Bacterial, Viral, and Non-infectious Origin of COPD Exacerbations. COPD. 2005;2(1):7-16. PubMed PMID: 17136956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A two-stage logistic model based on the measurement of pro-inflammatory cytokines in bronchial secretions for assessing bacterial, viral, and non-infectious origin of COPD exacerbations. AU - Dal Negro,Roberto W, AU - Micheletto,Claudio, AU - Tognella,Silvia, AU - Visconti,Marilia, AU - Guerriero,Massimo, AU - Sandri,Marco F, PY - 2006/12/2/pubmed PY - 2007/2/23/medline PY - 2006/12/2/entrez SP - 7 EP - 16 JF - COPD JO - COPD VL - 2 IS - 1 N2 - UNLABELLED: Exacerbations often complicate the progressive course of chronic obstructive pulmonary disease (COPD), mainly due to infectious agents. The precise role of bacterial infections in the course and the pathogenesis of COPD has been a source of controversy for decades. Also viruses and other non-infectious causes of exacerbation play a relevant role and also contribute to persisting airway inflammation. Usually, the etiologic identification of the infective causes of COPD require considerable time and costs. The development of more rapid, reliable, and widely applicable methods to promptly define the etiology of COPD exacerbations should represent a relevant issue in devising earlier and more specific strategies for their effective therapeutic control. AIM: Of the study was to assess the predictive role of some pro-inflammatory cytokines measured in spontaneous bronchial secretions in discriminating the main infectious causes of COPD exacerbations. METHODS: 124 subjects with moderate COPD (51-79 y; mean basal FEV1 = 49.6% pred. +/- 4.6 sd; FEV1 reversibility +3.9% from baseline +/- 4.8 sd after salbutamol 200 mcg) were studied during acute exacerbation. Respiratory viruses were isolated from bronchial secretions in 21 cases; common bacteria (CFU > or = 10(6)/ml) in 28 cases; Pseudomonas Aeruginosa (Ps.Ae.; CFU > or = 10(6)/ml) in 20 cases. The cytokines IL1beta, IL8, and TNFalpha (pg/ml; Immulite; Diagnostic Product Corp, Los Angeles, CA, USA), and neutrophils (% total count) were measured in bronchial secretions of all patients. STATISTICS: A two-stage logistic model was chosen for discriminating the different causes of COPD exacerbations (such as: non-infectious, or viral, bacterial, or due to Ps.Ae.). RESULTS: At the first decisional step, the two-stage logistic model proved that TNFalpha levels in bronchial secretions recognise clearly patients belonging to the Ps.Ae. group from those of all other groups (Area under ROC curve = 0.96; 95% CI = 0.91-0.99), and that, at the second decisional step, IL8 + IL10 levels discriminate patients with bacterial causes (such as all bacteria) from the non-infected ones and from those with a viral cause of exacerbation (Area under ROC curve = 0.87; 95% CI = 0.77-0.94). Neutrophil percent count did not support any contribution in discriminating the different subgroups of COPD subjects. CONCLUSIONS: When exacerbated, COPD subjects express different patterns of pro-inflammatory mediators in bronchial secretions, which appear modulated according to the etiological cause of the exacerbation. In particular, TNFalpha concentration per se enables recognition of COPD exacerbations due to Ps.Ae., while IL8 + IL1beta levels prove helpful in discriminating those to common bacteria from those to viral agents and to non-infectious causes. When present data are further confirmed, the use of a decisional rule based on cytokine measurements might be regarded as a helpful predictive tool. As measures of pro-inflammatory cytokines are low-cost, simple, and faster to perform, they could support rapid clinical decision making at the bedside regarding therapeutic strategy for COPD exacerbations, in particular when they are needed for severe COPD patients. SN - 1541-2555 UR - https://www.unboundmedicine.com/medline/citation/17136956/A_two_stage_logistic_model_based_on_the_measurement_of_pro_inflammatory_cytokines_in_bronchial_secretions_for_assessing_bacterial_viral_and_non_infectious_origin_of_COPD_exacerbations_ L2 - https://medlineplus.gov/copd.html DB - PRIME DP - Unbound Medicine ER -