Inflammatory Profile of New Bacterial Strain Exacerbations of Chronic Obstructive Pulmonary Disease

Sethi, Sanjay; Wrona, Catherine; Eschberger, Karen; Lobbins, Phyllis; Cai, Xueya; Murphy, Timothy F.

doi:10.1164/rccm.200708-1234oc

Cited by 164 publications

(153 citation statements)

References 34 publications

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“…When airway and systemic inflammation during new strain exacerbations are compared with exacerbations without new bacterial strains, a greater intensity of neutrophilic airway inflammation and systemic inflammation is demonstrated in the former group [15]. Furthermore, WHITE et al [16] have shown that clearance of bacteria following 10 days of treatment with antibiotics for purulent sputum exacerbations was associated with a reduction in neutrophilic inflammation, while bacterial persistence was associated with persistent elevation of airway inflammation.…”

Section: Mechanisms Of Bacterial Pathogenesis In Copdmentioning

confidence: 99%

Infection as a comorbidity of COPD

2010

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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: Mechanisms Of Bacterial Pathogenesis In Copdmentioning

confidence: 99%

Infection as a comorbidity of COPD

2010

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“…Exacerbations are major drivers of morbidity, mortality, and health care use in chronic obstructive pulmonary disease (COPD) (1)(2)(3). Most exacerbations are triggered by bacterial or viral infections (4), or by acquisition of a new strain of a colonizing bacterium (1,2).…”

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confidence: 99%

“…Most exacerbations are triggered by bacterial or viral infections (4), or by acquisition of a new strain of a colonizing bacterium (1,2). Nonencapsulated or nontypeable Haemophilus influenzae (NTHi) can be isolated in up to 80 to 87% of COPD exacerbations (5,6) and is the most common bacteria colonizing the airways in COPD (6), with colonization correlated with exacerbations, severity of airway inflammation (5), and symptoms (2,6).…”

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confidence: 99%

Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection

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Wallington²,

Williams

et al. 2016

Am J Respir Crit Care Med

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Rationale: Mucosal-associated invariant T (MAIT) cells are a recently described abundant, proinflammatory T-cell subset with unknown roles in pulmonary immunity. Nontypeable Haemophilus influenzae (NTHi) is the leading bacterial pathogen during chronic obstructive pulmonary disease (COPD) exacerbations and is a plausible target for MAIT cells.Objectives: To investigate whether MAIT cells respond to NTHi and the effects of inhaled corticosteroids (ICS) on their frequency and function in COPD.Methods: Eleven subjects with COPD receiving ICS, 8 steroid-naive subjects with COPD, and 21 healthy control subjects underwent phlebotomy, sputum induction, bronchoalveolar lavage, and endobronchial biopsy. Pulmonary and monocyte-derived macrophages were cultured in vitro with NTHi.Measurements and Main Results: Frequencies of Va7.2 1 CD161 1 MAIT cells, surface expression of the major histocompatibility complex-related protein 1 (MR1), and intracellular IFN-g expression were measured by flow cytometry. MAIT-cell frequencies were reduced in peripheral blood of ICStreated subjects with COPD (median 0.38%; interquartile range [IQR], 0.25-0.96) compared with healthy control subjects (1.8%; IQR, 1.4-2.5; P = 0.001) or steroid-naive patients with COPD (1.8%; IQR, 1.2-2.3; P = 0.04). MAIT cells were reduced in bronchial biopsies from subjects with COPD treated with steroids (0.73%; IQR, 0.46-1.3) compared with healthy control subjects (4.0%; IQR, 1.6-5.0; P = 0.02). Coculture of live NTHi increased macrophage surface expression of MR1 and induced IFN-g from CD4 cells and CD8 cells, but most potently from MAIT cells (median IFN-g-positive frequencies, 2.9, 8.6, and 27.6%, respectively). In vitro fluticasone and budesonide reduced MR1 surface expression twofold and decreased NTHi-induced IFN-g secretion eightfold.Conclusions: MAIT cells are deficient in blood and bronchial tissue in steroid-treated, but not steroid-naive, COPD. NTHi constitutes a target for pulmonary MAIT-cell immune responses, which are significantly impaired by corticosteroids.

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“…In further support of the vicious circle hypothesis, exacerbations of COPD in association with a new bacterial strain are associated with increases in systemic and local inflammatory mediators, including serum C-reactive protein and sputum TNF-a and neutrophil elastase. These increases were higher than those seen in exacerbations associated with preexisting bacteria or with pathogen-negative exacerbations (14).…”

Section: Infection In Copd: the Role Of Nontypeable H Influenzaementioning

confidence: 60%

Infections in “Noninfectious” Lung Diseases

et al. 2014

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Many chronic pulmonary diseases, including those that are not primarily infectious in etiology, have some aspects of their pathogenesis that are influenced by infectious organisms. Microorganisms may contribute to chronic lung diseases, either directly (i.e., overt infection) or indirectly, via the amplification of inflammatory pathways that are critical to host defense. As techniques for detecting and characterizing microorganisms have advanced, investigations of both infecting and colonizing organisms have yielded new insights into mechanisms of pulmonary disease. In addition, changes in patterns of infection and microbial resistance have important implications for treatment. Examples of these infectious-pulmonary associations, including Haemophilus influenzae infection and chronic obstructive pulmonary disease, nontuberculous mycobacteria and bronchiectasis, and human immunodeficiency virus and obstructive lung disease, are reviewed.

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Inflammatory Profile of New Bacterial Strain Exacerbations of Chronic Obstructive Pulmonary Disease

Abstract: Neutrophilic airway inflammation and systemic inflammation are more intense with well-defined bacterial exacerbations than with nonbacterial exacerbations. Clinical course of exacerbation and inflammation are closely linked.

Cited by 164 publications

References 34 publications

Infection as a comorbidity of COPD

Infection as a comorbidity of COPD

Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection

Infections in “Noninfectious” Lung Diseases

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