Haemophilus parainfluenzae infection of respiratory mucosa

Middleton, Andrew M.; Dowling, R.B.; Mitchell, Joanne; Watanabe, Shinichi; Rutman, A; Pritchard, K.; Tillotson, Glenn; Hill, Susan L.; Wilson, Robert

doi:10.1053/rmed.2002.1454

Cited by 21 publications

(15 citation statements)

References 25 publications

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“…These observations suggest that colonisation by these PPMs is already able to induce an inflammatory response in the bronchial mucosa of such patients. This inflammatory response was seen to be species-specific because in our series, a similar effect was not found in COPD patients colonised by H. parainfluenzae, a PPM that occasionally causes COPD exacerbation and pneumonia [29][30][31], but has been shown to exhibit low mucosal adherence and a minimal potential to cause bronchial inflammation [32,33]. Our choice of H. influenzae load as a main study variable was justified by its close relationship to the inflammatory response of the bronchial mucosa.…”

Section: Copd and Smoking-related Disorders A Marin Et Almentioning

confidence: 72%

Variability and effects of bronchial colonisation in patients with moderate COPD

Marín¹,

Monsó²,

García-Núñez³

et al. 2009

Eur Respir J

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Sputum and lung function were periodically assessed in stable moderate chronic obstructive pulmonary disease (COPD) outpatients to determine relationships between bronchial colonisation and inflammation.Relationships between potentially pathogenic microorganism (PPM) typology, bronchial inflammation (neutrophilia, tumour necrosis factor-a, interleukin (IL)-1b, IL-6, IL-8, IL-10 and IL-12) and post-bronchodilator decline in forced expiratory volume in 1 s (FEV1) were analysed. PPMs periodically showing the same molecular profile using pulse field gel electrophoresis were considered long-term persistent.Bronchial colonisation was observed in 56 out of 79 follow-up examinations (70.9%) and was mainly due to Haemophilus influenzae, Pseudomonas aeruginosa and enterobacteria (n547). These PPMs were all related to sputum neutrophilia (pf0.05, Chi-squared test), and H. influenzae was related to higher levels of IL-1b (p50.005) and IL-12 (p50.01), with a dose-response relationship (Spearman's correlation coefficient of 0.38 for IL-1b (p50.001), and of 0.32 for IL-12 (p50.006)). Haemophilus parainfluenzae was not associated with an identifiable inflammatory response. Long-term persistence of the same strain was observed in 12 examinations (21.4%), mainly due to P. aeruginosa or enterobacteria. A neutrophilic bronchial inflammatory response was associated with a statistically significant decline in FEV1 during follow-up (OR 2.67, 95% CI 1.07-6.62).A load-related relationship to bronchial inflammation in moderate COPD was observed for colonisation by H. influenzae, but not for colonisation by H. parainfluenzae.

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Section: Copd and Smoking-related Disorders A Marin Et Almentioning

confidence: 72%

Variability and effects of bronchial colonisation in patients with moderate COPD

Marín¹,

Monsó²,

García-Núñez³

et al. 2009

Eur Respir J

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“…The inclusion of H. parainfluenzae in the group of PPMs may be controversial; however, this microorganism was included in the original definition of PPMs [18] and has been considered a respiratory pathogen, together with H. influenzae, in many studies dealing with bacterial colonisation in COPD [6,7,9,18,28]. In fact, MIDDLETON et al [42] demonstrated that H. parainfluenzae can be a pathogen in the lower respiratory tract when impaired airway defences delay bacterial clearance, as is the case in COPD. In any case, the frequency of isolation of this microorganism, both at inclusion and at 8 weeks, was similar in both treatment groups; therefore, excluding this isolation from the analysis would have not modified the results.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD

Miravitlles

Marín²,

Monsó³

et al. 2009

Eur Respir J

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This study was designed to investigate the efficacy of moxifloxacin for the eradication of bacterial colonisation of the airways in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).Out of 119 stable patients with COPD screened, 40 (mean age 69 yrs, mean forced expiratory volume in 1 s 50% predicted) were colonised with potentially pathogenic microorganisms (PPMs) and were included in a randomised, double-blind, placebo-controlled trial with moxifloxacin 400 mg daily for 5 days.Eradication rates were 75% with moxifloxacin and 30% with placebo at 2 weeks (p50.01). Bacterial persistence at 8 weeks was still higher (not significantly) in the placebo arm (five (25%) out of 20 versus one (5%) out of 20; p50.18). The frequencies of acquisition of a new PPM were high and similar in both treatment groups; consequently, the prevalence of colonisation at 8 weeks was also similar between treatment arms. No difference was found in the number of patients with exacerbations during the 5-month follow-up. Only the acquisition of a new PPM during follow-up showed a statistically significant relationship with occurrence of an exacerbation.Moxifloxacin was effective in eradicating PPMs in patients with positive sputum cultures. However, most patients were recolonised after 8 weeks of follow-up. Acquisition of a new strain of bacteria was associated with an increased risk of developing an exacerbation.

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“…Several studies have been undertaken to investigate the interaction of respiratory pathogens and their virulence factors with airway epithelium [2]. A number of bacterial pathogens that colonize the airways and cause respiratory tract infections, such as Streptococcus pneumoniae , Haemophilus influenzae , Staphylococcus aureus , Klebsiella pneumoniae and Pseudomonas aeruginosa , among many others, have been shown to produce factors which affect the ciliated epithelium [4,5,6,7,8,9,10,11,12,13]. These virulence factors appear to play a role in the pathogenesis of respiratory tract infections by disturbing ciliary structure or function, by stimulating mucus production and by damaging the structural integrity of the epithelium, thus enhancing colonization [5].…”

Section: Innate Immune Mechanismsmentioning

confidence: 99%

Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System

et al. 2010

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In general antibiotics interact cooperatively with host defences, weakening and decreasing the virulence of microbial pathogens, thereby increasing vulnerability to phagocytosis and eradication by the intrinsic antimicrobial systems of the host. Antibiotics, however, also interact with host defences by several other mechanisms, some harmful, others beneficial. Harmful activities include exacerbation of potentially damaging inflammatory responses, a property of cell-wall targeted agents, which promotes the release of pro-inflammatory microbial cytotoxins and cell-wall components. On the other hand, inhibitors of bacterial protein synthesis, especially macrolides, possess beneficial anti-inflammatory/cytoprotective activities, which result from interference with the production of microbial virulence factors/cytotoxins. In addition to these pathogen-directed, anti-inflammatory activities, some classes of antimicrobial agent possess secondary anti-inflammatory properties, unrelated to their conventional antimicrobial activities, which target cells of the innate immune system, particularly neutrophils. This is a relatively uncommon, potentially beneficial property of antibiotics, which has been described for macrolides, imidazole anti-mycotics, fluoroquinolones, and tetracyclines. Although of largely unproven significance in the clinical setting, increasing awareness of the pro-inflammatory and anti-inflammatory properties of antibiotics may contribute to a more discerning and effective use of these agents.

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Haemophilus parainfluenzae infection of respiratory mucosa

Cited by 21 publications

References 25 publications

Variability and effects of bronchial colonisation in patients with moderate COPD

Variability and effects of bronchial colonisation in patients with moderate COPD

Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD

Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System

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