Relationship Between Bacterial Flora in Sputum and Functional Impairment in Patients With Acute Exacerbations of COPD

doi:10.1378/chest.116.1.40

Chest

Volume 116, Issue 1, July 1999, Pages 40-46

https://doi.org/10.1378/chest.116.1.40 Get rights and content

Study objectives

To investigate the possible relationship between functional respiratory impairment measured by FEV₁ and isolation of diverse pathogens in the sputum of patients with exacerbations of COPD.

Design

Multicenter, cross-sectional, epidemiologic study.

Setting

Pneumology units in six secondary or tertiary hospitals in Spain.

Patients

Ninety-one patients with acute exacerbation of COPD were included.

Interventions

A quantitative sputum culture was performed, and bacterial growth was considered significant only when the germ was isolated at concentrations > 10⁶ cfu (> 10⁵for Streptococcus pneumoniae) in samples with < 10 epithelial cells and > 25 leukocytes per low magnification field (×100).

Results

Germs isolated were the following: Haemophilus influenzae (20 cases; 22%), Pseudomonas aeruginosa (14 cases; 15%), S pneumoniae (9 cases; 10%), Moraxella catarrhalis (8 cases; 9%), other Gram-negative bacteria (7 cases; 7%), and non-potentially pathogenic microorganisms (non-PPMs; 33 cases; 36%). P aeruginosa and H influenzae were isolated more frequently among the patients with FEV₁ < 50% than among those with FEV₁ > 50% (p < 0.05). All patients with P aeruginosa in sputum had FEV₁ < 1,700 mL. FEV₁ < 50% was associated with a very high risk of P aeruginosa or H influenzae isolation: the odds ratios (ORs) are 6.62 (95% confidence interval [CI], 1.2 to 123.6) and 6.85 (95% CI, 1.6 to 52.6), respectively. Furthermore, active tobacco smoking was associated with a high risk of H influenzae isolation (OR, 8.1; 95% CI, 1.9 to 43.0).

Conclusions

Patients with the greatest degree of functional impairment, as measured by their FEV₁, presented a higher probability of having an isolation of P aeruginosa or H influenzae in significant concentrations in sputum during an exacerbation. The diagnostic yield of sputum in patients with an FEV₁ > 50% was low, with a predominance of non-PPMs. Low FEV₁ and active tobacco smoking are data that should be considered when establishing an empiric antibiotic treatment for exacerbated COPD.

Section snippets

Materials and Methods

This study was a multicenter, cross-sectional, epidemiologic study conducted to identify isolated bacteria in the sputum of exacerbated COPD patients and to relate them to the degree of functional impairment, as measured by the FEV₁.

Population Characteristics

Data were collected from 148 patients over the study period. Forty-nine patients for whom it proved impossible to obtain a valid sputum sample were excluded. Of the 99 remaining patients, 8 patients (8%) were declared invalid for failing to comply with protocol inclusion or exclusion criteria. In six cases, the FEV₁/FVC coefficient was > 70%. In one case, the spirometry provided was > 6 months old, and in another case, the bronchodilator test was positive, with FEV₁ > 80% predicted. Thus, 91

Discussion

The results of this study suggest that the degree of functional respiratory impairment of COPD patients indicates the presence of different PPMs in their sputum samples in the course of an exacerbation. Individuals with severe pulmonary function impairment, manifested by FEV₁ < 50% predicted, are at a sixfold higher risk of suffering acute exacerbations caused by H influenzae or P aeruginosa than are patients presenting with FEV₁ > 50%. In milder patients with FEV₁ > 50%, the sputum culture was

Coordinators

Marc Miravitlles, MD, Pneumology Department, Hospital Vall d'Hebron, Barcelona, Spain; and Cristina Espinosa, MD, RD Department, QF Bayer, Barcelona, Spain.

Participating Investigators

E. Fernández-Laso, MD, Hospital Magdalena, Castellón, Spain; J.A. Maldonado, MD, R. Ayerbe García, MD, and M. Gómez Entrena, MD, Hospital Juan Ramón Jiménez, Huelva, Spain; J.A. Martos, MD, Hospital San Rafael, Barcelona, Spain; E. Balcells, MD, and G. Levy, MD, Hospital Vall d'Hebron, Barcelona, Spain; E. Marquilles, MD, and E. Martín, MD,

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Cited by (403)

Chronic Bronchial Infection in Stable COPD
2023, Open Respiratory Archives
Clásicamente el papel de la infección pulmonar en el paciente con enfermedad pulmonar obstructiva crónica (EPOC) se ha centrado en los periodos de agudización. Sin embargo, en fase de estabilidad clínica, se ha prestado poca atención al papel que pueden jugar la presencia de microorganismos potencialmente patógenos (MPP) (en especial de forma repetida, lo que se conoce como infección bronquial crónica [IBC]) en la patogenia, pronóstico y tratamiento de la enfermedad. En los últimos años, sin embargo, se han ido acumulando algunas evidencias sobre el efecto deletéreo de esta situación. La IBC en EPOC se ha asociado a una mayor inflamación local, mayor gravedad de la enfermedad, peor calidad de vida relacionada con la salud, mayor número y gravedad de agudizaciones y eventos cardiovasculares, la presencia de bronquiectasias, una pérdida acelerada de función pulmonar e incluso mayor mortalidad (en especial cuando es Pseudomonas aeruginosa (PA) el microorganismo causante de la infección). No se conoce, sin embargo, cuál es el papel que el tratamiento antiinflamatorio o antibiótico de esta infección pueda tener. La presente revisión repasa la evidencia científica existente sobre la IBC en la EPOC estable, desde su propia definición hasta los posibles tratamientos. Asimismo se abordarán los numerosos retos futuros que genera, en especial el desarrollo en el conocimiento del microbioma pulmonar, sus alteraciones y sus consecuencias.
Classically, the role of pulmonary infection in patients with chronic obstructive pulmonary disease (COPD) has focused on periods of exacerbation. However, in a clinically stable situation, little attention has been paid to the role play by the presence of potentially pathogenic micro-organisms (especially when they are repeatedly isolated, which is known as chronic bronchial infection [CBI]) in the pathogenesis, prognosis and disease treatment. In recent years, however, some evidence has been published on the deleterious effect of CBI in COPD since it has been associated to greater local inflammation, greater disease severity, poorer health-related quality of life, greater number and severity of exacerbations and cardiovascular events, presence of bronchiectasis, rapid decline of lung function, and even higher mortality (especially related to Pseudomonas aeruginosa infection). It is not known, however, what is the role of anti-inflammatory or antibiotic treatments on CBI in stable COPD patients. This review focused on the scientific evidence on this topic that exists up to now, from the very definition of IBC in COPD to the possible treatments that this situation entails, as well as the numerous future challenges it generates, especially the development of knowledge of the pulmonary microbiome, its alterations and its consequences.
Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease
2022, Clinical Microbiology and Infection
It is unclear whether recurrent sputum culture with Pseudomonas aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and whether lineages genetically adapt during carriage.
Whole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142).
A total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated.
Recurrent P. aeruginosa was common and carried for a prolonged time after initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD are warranted.
Consensus Document on the Diagnosis and Treatment of Chronic Bronchial Infection in Chronic Obstructive Pulmonary Disease
2020, Archivos de Bronconeumologia
A pesar de que es conocido que la presencia crónica de microorganismos en las vías aéreas de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) en fase de estabilidad conlleva una evolución desfavorable, ninguna guía de manejo de la enfermedad establece pautas sobre cómo diagnosticar y tratar este tipo de casos.
Con la intención de orientar a los profesionales, desde la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) se ha elaborado un documento que pretende aportar respuestas clínicas sobre el manejo de pacientes con EPOC en los que se aíslan microorganismos de forma puntual o persistente. Dado que la heterogeneidad de las evidencias científicas disponibles no permite crear una Guía de Práctica Clínica, se ha elaborado un documento basado en la literatura científica existente y/o en la propia experiencia clínica que aborda tanto la definición de las diferentes situaciones clínicas como su diagnóstico y manejo. El texto ha sido consensuado entre un amplio número de neumólogos con gran experiencia clínica y científica en este ámbito. Este documento cuenta con el aval del Comité Científico de SEPAR.
Although the chronic presence of microorganisms in the airways of patients with stable chronic obstructive pulmonary disease (COPD) confers a poor outcome, no recommendations have been established in disease management guidelines on how to diagnose and treat these cases.
In order to guide professionals, the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has prepared a document which aims to answer questions on the clinical management of COPD patients in whom microorganisms are occasionally or habitually isolated. Since the available scientific evidence is too heterogeneous to use in the creation of a clinical practice guideline, we have drawn up a document based on existing scientific literature and clinical experience, addressing the definition of different clinical situations and their diagnosis and management. The text was drawn up by consensus and approved by a large group of respiratory medicine experts with extensive clinical and scientific experience in the field, and has been endorsed by the SEPAR Scientific Committee.
Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: an observational cohort study of 22 053 patients
2020, Clinical Microbiology and Infection
The role of Pseudomonas aeruginosa in the long-term prognosis of chronic obstructive pulmonary disease (COPD) is unknown. The purpose of this study was to determine whether P. aeruginosa is associated with increased risk of exacerbations or death in patients with COPD.
This is a multiregional epidemiological study based on complete data on COPD outpatients between 1 January 2010 and 31 October 2017 and corresponding microbiology and national register data. Time-dependent Cox proportional hazards models and propensity matching was used to estimate hospitalization-demanding exacerbations and death after 2 years, separately and in combination.
A total of 22 053 COPD outpatients were followed for a median of 1082 days (interquartile-range: 427–1862). P. aeruginosa was present in 905 (4.1%) patients. During 730 days of follow-up, P. aeruginosa strongly and independently predicted an increased risk of hospitalization for exacerbation or all-cause death (HR 2.8, 95%CI 2.2–3.6; p <0.0001) and all-cause death (HR 2.7, 95%CI 2.3–3.4; p <0.0001) in analyses adjusted for known and suspected confounders. The signal remained unchanged in unadjusted analyses as well as propensity-matched subgroup analyses. Among patients ‘ever colonized’ with P. aeruginosa, the incidence of hospital-demanding exacerbations doubled after the time of the first colonization.
COPD patients in whom P. aeruginosa can be cultured from the airways had a markedly increased risk of exacerbations and death. It is still not clear whether this risk can be reduced by offering patients targeted antipseudomonal antibiotics. A randomized trial is currently recruiting patients to clarify this (ClinicalTrials.gov: NCT03262142).
Antimicrobial Peptides in Lung Health and Pulmonary Diseases
2024, Lung Biology and Pathophysiology
The COPD-Associated Polymorphism Impairs the CFTR Function to Suppress Excessive IL-8 Production upon Environmental Pathogen Exposure
2023, International Journal of Molecular Sciences

View all citing articles on Scopus

: Study supported by QF Bayer, Spain.

^†: A complete list of coordinators and participating investigators forthe Study Group of Bacterial Infection in COPD is located in the Appendix.

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Chest

Clinical InvestigationsCOPDRelationship Between Bacterial Flora in Sputum and Functional Impairment in Patients With Acute Exacerbations of COPD

Study objectives

Design

Setting

Patients

Interventions

Results

Conclusions

Section snippets

Materials and Methods

Population Characteristics

Discussion

Coordinators

Participating Investigators

Respir Med

Arch Bronconeumol

Arch Bronconeumol

Lancet

Chest

Bacterial infection in chronic obstructive pulmonary disease

Am Rev Respir Dis

Infections of the airways

Curr Opin Infect Dis

Curse and prognosis of chronic obstructive lung disease

N Engl J Med

Use of investigations in lower respiratory tract infection in the community: a European survey

Eur Respir Dis

Characterization of distal bronchial microflora during acute exacerbations of chronic bronchitis

Am Rev Respir Dis

Bacterial infection in chronic obstructive pulmonary disease: a study of stable and exacerbated outpatients using the protected specimen brush

Am J Respir Crit Care Med

ERS consensus statement: optimal assessment and management of chronic obstructive pulmonary disease (COPD); a consensus statement of the European Respiratory Society (ERS)

Eur Respir J

Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Initial antibiotic therapy for lower respiratory tract infection in the community: a European survey

Eur Respir J

Clinical Investigations
COPD
Relationship Between Bacterial Flora in Sputum and Functional Impairment in Patients With Acute Exacerbations of COPD