Current Challenges in Chronic Bronchial Infection in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Currently, chronic obstructive pulmonary disease (COPD) patients and their physicians face a number of significant clinical challenges, one of which is the high degree of uncertainty related to chronic bronchial infection (CBI). By reviewing the current literature, several challenges can be identified, which should be considered as goals for research. One of these is to establish the bases for identifying the biological and clinical implications of the presence of potentially pathogenic microorganisms in the airways that should be more clearly elucidated according to the COPD phenotype. Another urgent area of research is the role of long-term preventive antibiotics. Clinical trials need to be carried out with inhaled antibiotic therapy to help clarify the profile of those antibiotics. The role of inhaled corticosteroids in patients with COPD and CBI needs to be studied to instruct the clinical management of these patients. Finally, it should be explored and confirmed whether a suitable antimicrobial treatment during exacerbations may contribute to breaking the vicious circle of CBI in COPD. The present review addresses the current state of the art in these areas to provide evidence which will enable us to progressively plan better healthcare for these patients.

Comorbid Conditions in Chronic Obstructive Pulmonary Disease: Potential Therapeutic Targets for Unmet Needs

“…Microorganisms are frequently observed in the airways of COPD patients, both in stable state and during exacerbations. The isolation of potentially pathogenic microorganisms (PPM) such as Hemophilus influenzae , Streptococcus pneumoniae , or Pseudomonas aeruginosa from respiratory samples does not fit the definition of colonization, since it is associated with tissue damage and an inflammatory response [ 24 , 25 ]. Recently, a clinical feature of chronic bronchial infection (CBI) has been suggested to be the appearance of the same PPM in at least three sputum cultures in a year, each separated by at least a month [ 26 ].…”

“…It is well recognized that there is a strong association between CBI and COPD exacerbations. Most patients with CBI and frequent bacterial exacerbations produce colored/purulent sputum even in the stable state, have more severe dyspnea and an impaired quality of life, and may fulfill radiological criteria for bronchiectasis in chest CTs [ 24 , 25 , 26 , 27 ]. Interestingly, a recent prospective study reported that the presence of chronic purulent sputum, number of PPM isolations, and hospitalizations due to the exacerbation of COPD are independent risk factors of bronchiectasis progression in patients with moderate-to-severe COPD [ 28 ].…”

“…In many previous studies, the regular use of macrolides (e.g., erythromycin, clarithromycin, and azithromycin) has been shown to reduce emergency room visits and hospitalization due to exacerbations of COPD [ 22 , 23 , 24 ]. The mechanisms of the therapeutic effects of macrolide can go beyond their direct anti-microbial effects; the latest data show that they exert multiple effects on the structure and composition of the lower airway microbiota, with an increased production of bacterial metabolites with anti-inflammatory properties [ 22 , 24 ]. Azithromycin use can reduce the risk of COPD exacerbations, but is also associated with increased incidence of colonization with macrolide-resistant organisms, an excessive rate of hearing decrements, and the prolongation of the QTc interval [ 23 ].…”

“…However, treatable conditions that are not recognized as therapeutic targets may be latent in patients with COPD. However, there is accumulating evidence indicating that some clinical features and specific biomarkers can be used to identify patients who should be given second controllers, such as inhaled corticosteroids (ICS) [ 16 , 17 , 18 ], selective β1-blockers [ 19 , 20 , 21 ], and macrolides [ 22 , 23 , 24 ]. We again realized that treatable traits should be assessed and treated as early as possible [ 9 ].…”

<p>A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future</p>

“…51 Colonization implies no harm to the host, and, by definition, it would not require any type of treatment, but PPMs in stable COPD are associated with increased inflammation, increased frequency and severity of exacerbations and faster decline in pulmonary function; therefore, the term colonization is no longer considered adequate. 52 Regarding the treatment of chronic bronchial infection in chronic airway diseases, there is limited experience in asthma and COPD. The isolation of Pseudomonas aeruginosa has been shown to be associated to a greater risk of exacerbation in asthma, and the AMAZES study evidenced that azithromycin at a dose of 500 mg 3 times a week, as a treatment added to the usual medication, is capable of reducing severe exacerbations and improving the quality of life of poorly controlled asthmatics despite a combination of ICS/LABA.…”