Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease

Respiratory Research

Jadwiga A Wedzicha¹  Gavin C Donaldson¹  Peter J Barnes¹  Louise E Donnelly¹  Simon E Brill¹  Beverly S Kowlessar¹  Davinder S Garcha²  Anant RC Patel²  Alexander J Mackay²  Richa Singh¹ 

[1] Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LR, UK;Centre for Respiratory Medicine, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK

关键词: Colonisation;    Bacteria;    Inflammation;    COPD;   

Others  :  1137269
DOI  :  10.1186/s12931-014-0114-1

 received in 2014-06-27, accepted in 2014-09-02,  发布年份 2014

【 摘 要 】

Background

There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.

Methods

We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012. Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.

Results

Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively). Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05). Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads. Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs. No association was observed between inflammation and health status (p > 0.05).

Conclusions

Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique. The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae. However, discordance between inflammation and health status was observed.

【 授权许可】

   
2014 Singh et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Wedzicha JA, Seemungal TA, MacCallum PK, Paul EA, Donaldson GC, Bhowmik A, Jeffries DJ, Meade TW: Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels. Thromb Haemost 2000, 84:210-215.
• [2]Hurst JR, Perera WR, Wilkinson TM, Donaldson GC, Wedzicha JA: Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006, 173:71-78.
• [3]Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R: Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease, GOLD Executive Summary. Am J Respir Crit Care Med 2013, 187:347-365.
• [4]Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, et al.: Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012, 380:2095-2128.
• [5]Wedzicha JA, Seemungal TAR: COPD exacerbations: defining their cause and prevention. The Lancet 2007, 370:786-796.
• [6]Patel IS, Seemungal TA, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA: Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002, 57:759-764.
• [7]Banerjee D, Khair OA, Honeybourne D: Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD. Eur Respir J 2004, 23:685-691.
• [8]Rosell A, Monso E, Soler N, Torres F, Angrill J, Riise G, Zalacain R, Morera J, Torres A: Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease. Arch Intern Med 2005, 165:891-897.
• [9]Sethi S, Murphy TF: Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 2008, 359:2355-2365.
• [10]Hill AT, Campbell EJ, Hill SL, Bayley DL, Stockley RA: Association between Airway Bacterial Load and Markers of Airway Inflammation in Patients with Stable Chronic Bronchitis. Am J Med 2000, 109:288-295.
• [11]Sethi S, Maloney J, Grove L, Wrona C, Berenson CS: Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006, 173:991-998.
• [12]Marin A, Garcia-Aymerich J, Sauleda J, Belda J, Millares L, Garcia-Nunez M, Serra I, Benet M, Agusti A, Anto JM, Monso E: Effect of Bronchial Colonisation on Airway and Systemic Inflammation in Stable COPD. Copd 2012, 9:121-130.
• [13]Wilkinson TM, Patel IS, Wilks M, Donaldson GC, Wedzicha JA: Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003, 167:1090-1095.
• [14]Staley JT, Konopka A: Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu Rev Microbiol 1985, 39:321-346.
• [15]Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, Young VB, Toews GB, Curtis JL, Sundaram B, Martinez FJ, Huffnagle GB: Analysis of the lung microbiome in the “healthy” smoker and in COPD. PLoS One 2011, 6:e16384.
• [16]Garcha DS, Thurston SJ, Patel AR, Mackay AJ, Goldring JJ, Donaldson GC, McHugh TD, Wedzicha JA: Changes in prevalence and load of airway bacteria using quantitative PCR in stable and exacerbated COPD. Thorax 2012, 67:1075-1080.
• [17]Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA: Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998, 157:1418-1422.
• [18]Jones PW, Quirk FH, Baveystock CM, Littlejohns P: A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis 1992, 145:1321-1327.
• [19]Bhowmik A, Seemungal TA, Sapsford RJ, Devalia JL, Wedzicha JA: Comparison of spontaneous and induced sputum for investigation of airway inflammation in chronic obstructive pulmonary disease. Thorax 1998, 53:953-956.
• [20]Wilkinson TM, Hurst JR, Perera WR, Wilks M, Donaldson GC, Wedzicha JA: Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD. Chest 2006, 129:317-324.
• [21]Stockley RA, Bayley D, Hill SL, Hill AT, Crooks S, Campbell EJ: Assessment of airway neutrophils by sputum colour: correlation with airways inflammation. Thorax 2001, 56:366-372.
• [22]Matkovic Z, Miravitlles M: Chronic bronchial infection in COPD. Is there an infective phenotype? Respir Med 2013, 107:10-22.
• [23]Fuschillo S, Martucci M, Donner CF, Balzano G: Airway bacterial colonization: the missing link between COPD and cardiovascular events? Respir Med 2012, 106:915-923.
• [24]Duvoix A, Dickens J, Haq I, Mannino D, Miller B, Tal-Singer R, Lomas DA: Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease. Thorax 2013, 68:670-676.
• [25]N'Guessan PD, Haarmann H, Steiner T, Heyl K, Schreiber F, Heinrich A, Slevogt H: The Moraxella catarrhalis-induced pro-inflammatory immune response is enhanced by the activation of the epidermal growth factor receptor in human pulmonary epithelial cells. Biochem Biophys Res Commun 2014, 450:1038-1044.
• [26]King P: Haemophilus influenzae and the lung (Haemophilus and the lung). Clin Transl Med 2012, 1:10. BioMed Central Full Text
• [27]Read RC, Wilson R, Rutman A, Lund V, Todd HC, Brain AP, Jeffery PK, Cole PJ: Interaction of nontypable Haemophilus influenzae with human respiratory mucosa in vitro. J Infect Dis 1991, 163:549-558.
• [28]Desai H, Eschberger K, Wrona C, Grove L, Agrawal A, Grant B, Yin J, Parameswaran GI, Murphy T, Sethi S: Bacterial colonization increases daily symptoms in patients with chronic obstructive pulmonary disease. Ann Am Thorac Soc 2014, 11:303-309.
• [29]Marin A, Monso E, Garcia-Nunez M, Sauleda J, Noguera A, Pons J, Agusti A, Morera J: Variability and effects of bronchial colonisation in patients with moderate COPD. Eur Respir J 2010, 35:295-302.
• [30]Murphy TF, Brauer AL, Schiffmacher AT, Sethi S: Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004, 170:266-272.
• [31]Sethi S, Evans N, Grant BJ, Murphy TF: New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med 2002, 347:465-471.
• [32]Patel IS, Vlahos I, Wilkinson TM, Lloyd-Owen SJ, Donaldson GC, Wilks M, Reznek RH, Wedzicha JA: Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004, 170:400-407.
• [33]Martinez-Garcia MA, Soler-Cataluna JJ, Donat Sanz Y, Catalan Serra P, Agramunt Lerma M, Ballestin Vicente J, Perpina-Tordera M: Factors associated with bronchiectasis in patients with COPD. Chest 2011, 140:1130-1137.