Persistent Colonization by <i>Haemophilus influenzae</i> in Chronic Obstructive Pulmonary Disease

Murphy, Timothy F.; Brauer, Aimee L.; Schiffmacher, Andrew T.; Sethi, Sanjay

doi:10.1164/rccm.200403-354oc

Cited by 256 publications

(243 citation statements)

References 34 publications

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“…Molecular detection, however, established that strain-specific H. influenzae DNA was detected in the majority of the sputum samples that had yielded negative cultures, demonstrating persistent infection [43]. Similar observations have now been made for P. aeruginosa, implying that sputum cultures underestimate the frequency of bacterial colonisation in COPD.…”

Section: Chronic Infection In Copdsupporting

confidence: 59%

“…However, the appropriate definition of colonisation is the presence of a pathogen that does not cause damaging effects to the host or elicit a host response. In contrast, several recent studies show that bacterial pathogens are associated with host inflammatory and immune responses in stable COPD [40][41][42][43][44][45][46]. These findings suggest that application of the term colonisation to the lower airway bacterial presence in COPD is a misnomer, because it is likely that it is a low-grade chronic infection, with significant pathophysiological consequences.…”

Section: Chronic Infection In Copdmentioning

confidence: 94%

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Infection as a comorbidity of COPD

Sethi

2010

European Respiratory Journal

209

166

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The normal lung has several defence mechanisms to deal with microorganisms. Lower respiratory infections in the absence of lung disease are therefore relatively infrequent as compared with upper respiratory tract infections in healthy adults. In the setting of chronic obstructive pulmonary disease (COPD), lower respiratory tract infections, both acute and chronic, occur with increased frequency. As these infections contribute considerably to the clinical course of the patient with COPD, they constitute a significant comorbidity in COPD. Recurrent acute infections by bacterial and/or viral pathogens are now clearly linked with the occurrence of exacerbations of COPD. In addition, the occurrence of pneumonia in COPD has received considerable recent attention as it appears to be increased by the use of inhaled corticosteroids. The role of chronic infection in the pathogenesis of COPD is an active area of research with several different types of pathogens potentially implicated. Additionally, COPD patients with HIV infection have a more rapidly progressive decline in lung function than non-HIV-infected patients. Enhanced understanding of the host-pathogen interaction is needed to better prevent and treat respiratory tract infection in COPD.

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Section: Chronic Infection In Copdsupporting

confidence: 59%

Section: Chronic Infection In Copdmentioning

confidence: 94%

Infection as a comorbidity of COPD

Sethi

2010

European Respiratory Journal

209

166

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“…It is well known that a negative sputum culture does not rule out bacterial infection [29]. In fact, studies using invasive techniques in more severe, hospitalised patients, such as the protected specimen brush method, have demonstrated the high prevalence of bacteria in patients with coloured sputum [16], which is more reliable than the percentage of positive cultures.…”

Section: Discussionmentioning

confidence: 99%

Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis

Miravitlles

Kruesmann²,

Haverstock³

et al. 2011

Eur Respir J

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We examined the correlation between sputum colour and the presence of potentially pathogenic bacteria in acute exacerbations of chronic bronchitis (AECBs).Data were pooled from six multicentre studies comparing moxifloxacin with other antimicrobials in patients with an AECB. Sputum was collected before antimicrobial therapy, and bacteria were identified by culture and Gram staining. Association between sputum colour and bacteria was determined using logistic regression.Of 4,089 sputum samples, a colour was reported in 4,003; 1,898 (46.4%) were culture-positive. Green or yellow sputum samples were most likely to yield bacteria (58.9% and 45.5% of samples, respectively), compared with 18% of clear and 39% of rust-coloured samples positive for potentially pathogenic microorganisms. Factors predicting a positive culture were sputum colour (the strongest predictor), sputum purulence, increased dyspnoea, male sex and absence of fever. Green or yellow versus white sputum colour was associated with a sensitivity of 94.7% and a specificity of 15% for the presence of bacteria.Sputum colour, particularly green and yellow, was a stronger predictor of potentially pathogenic bacteria than sputum purulence and increased dyspnoea in AECB patients. However, it does not necessarily predict the need for antibiotic treatment in all patients with AECB.

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“…An opportunistic pathogen, NTHI resides asymptomatically in the upper airways of humans but can disseminate into privileged anatomical locations, causing infections such as otitis media, sinusitis, and pneumonia (47). NTHI is also one of the most prevalent microorganisms found in the lungs of patients with exacerbations of chronic obstructive pulmonary disease (48,49,60) and cystic fibrosis (23,43,58). An effective vaccine against NTHI strains has not yet been discovered, likely due to high variability of surface antigens between strains (60).…”

mentioning

confidence: 99%

A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model

et al. 2011

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Nontypeable Haemophilus influenzae (NTHI) is a Gram-negative bacterial pathogen that causes upper and lower respiratory infections. Factors required for pulmonary infection by NTHI are not well understood. Previously, using high-throughput insertion tracking by deep sequencing (HITS), putative lung colonization factors were identified. Also, previous research indicates that secreted disulfide-dependent factors are important for virulence of H. influenzae. In the present study, HITS data were compared with an informatics-based list of putative substrates of the periplasmic oxidoreductase DsbA to find and characterize secreted virulence factors. This analysis resulted in identification of the "zinc binding essential for virulence" (zev) locus consisting of zevA (HI1249) and zevB (HI1248). NTHI mutants of zevA and zevB grew normally in rich medium but were defective for colonization in a mouse lung model. Mutants also exhibited severe growth defects in medium containing EDTA and were rescued by supplementation with zinc. Additionally, purified recombinant ZevA was found to bind to zinc with high affinity. Together, these data demonstrate that zevAB is a novel virulence factor important for zinc utilization of H. influenzae under conditions where zinc is limiting. Furthermore, evidence presented here suggests that zinc limitation is likely an important mechanism for host defense against pathogens during lung infection.

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Persistent Colonization by Haemophilus influenzae in Chronic Obstructive Pulmonary Disease

Cited by 256 publications

References 34 publications

Infection as a comorbidity of COPD

Infection as a comorbidity of COPD

Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis

A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model

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