European Respiratory Society
The Spectrum of Bronchial Infection

Lower respiratory tract infections are one the most frequent causes of medical consultation in primary care. They are also one of the main causes of emergency visits and hospital admissions. The majority of these infections occur in the bronchial tree and include a large spectrum of aetiologies and clinical manifestations, from mild acute bronchitis to severe bronchiectasis and exacerbations of chronic obstructive pulmonary disease. In this Monograph, a series of prestigious researchers and clinicians provide an overview of the advances in the pathogenesis, manifestations and new approaches to treatment of bronchial infection in a wide variety of clinical scenarios. This book offers the reader the best existing scientific evidence that can be applied to the care of patients with any kind of bronchial infection.

  • European Respiratory Society Monographs
  1. Page v
  2. Page vii
  3. Page ix
  4. Page 1
    Correspondence: C. Llor, University Rovira i Virgili, Primary Care Centre Jaume I, c. Felip Pedrell 45–47, 43005 Tarragona, Spain. Email:

    Acute bronchitis is an inflammation of the tracheobronchial tree that occurs most commonly during the winter months and is associated with respiratory viruses. The role of bacteria in this infection is controversial, as bronchial biopsies have never demonstrated bacterial invasion. Treatment is generally symptomatic, directed at the relief of troublesome respiratory symptoms, particularly cough. Most of these lower respiratory tract infections are self-limiting and several studies suggest that antimicrobial treatment does not significantly shorten the duration of cough. However, many patients are prescribed antibiotics, mainly when discoloured sputum is present. Approaches to controlling acute cough have included narcotic cough suppressants, expectorants, mucolytics, antihistamines, decongestants, β2-agonists, analgesics, nonsteroidal anti-inflammatory drugs and herbal remedies. Despite the fact that these drugs are widely prescribed, there is little evidence that their routine use is helpful for adults with cough. However, guidelines suggest that a short trial of an antitussive medication, mainly dextromethorphan, may be reasonable, as well as β2-agonists in adults with bronchial obstruction.

  5. Page 18
    Correspondence: A. Anzueto, South Texas Veterans Health Care System, Audie L. Murphy Division at San Antonio, 7400 Merton Minter Boulevard (11C6), San Antonio, TX 78229, USA. Email:

    Chronic bronchitis is a clinical entity characterised by chronic bronchial mucus hypersecretion. It is frequently associated with chronic obstructive pulmonary disease (COPD) and it is related to worse outcomes. COPD patients with chronic bronchitis experienced accelerated lung function decline and an increased risk of exacerbations. Chronic mucus hypersecretion is also associated with acute or chronic bacterial bronchial infection, and increased airway and systemic inflammation. In addition, different antibiotic and anti-inflammatory treatments have been tested in these patients, with conflicting results. Mechanisms to explain the relationship between chronic bronchitis and infection are not well established, although host factors have been identified as key factors in the pathogenesis of bronchial infection. This chapter discusses the association of chronic bronchitis and the risk of bronchial infection, and the infection mechanisms that are responsible for this association, potential antibiotic and anti-inflammatory treatment.

  6. Page 27
    Correspondence: R.A. Stockley, ADAPT Project, Queen Elizabeth Hospital Birmingham, Edgbaston, B15 2WB, UK. Email:

    With the advent of increasing technology, reliance on simple clinical observation has become generally downgraded. However, direct observation and monitoring of sputum colour in patients with and without chronic bronchitis in the stable state and changes during exacerbations provides useful insights into the underlying pathology, nature of any acute exacerbation and the need for antibiotic therapy. Although subjective descriptions can generally be used to withhold antibiotic therapy for acute exacerbations, direct observation and objective grading is more reliable and helps in the delivery of patient directed self-management.

  7. Page 34
    Correspondence: S. Sethi, VA Western New York HealthCare System, 3495 Bailey Avenue, Buffalo, NY 14215, USA. Email:

    Chronic lung diseases that have prominent airway pathology accompanied by a change in the microbial flora of the lung include cystic fibrosis (CF), non-CF associated bronchiectasis, diffuse panbronchiolitis and chronic obstructive pulmonary disease (COPD). The presence of microbial pathogens in the lower airway has been demonstrated in several different ways to have damaging effects in these diseases, and is not innocuous colonisation. Bacterial and host mechanisms contribute to the pathogenesis of this chronic infection, especially disruption in innate lung defence. Several such defects in innate lung defence have been recently described in COPD, including impairment of mucociliary clearance and macrophage function, as well as deficiencies in immunoglobulin A and antimicrobial peptides. Important bacterial persistence mechanisms include host cell invasion, biofilm formation and antigenic alteration.

  8. Page 46
    Correspondence: Marc. Miravitlles, Servei de Pneumologia, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 119-129, 08035 Barcelona, Spain. Email:

    Impaired host defences in chronic bronchial diseases allow the establishment and proliferation of potentially pathogenic microorganisms (PPMs). This is particularly frequent in patients with chronic obstructive pulmonary disease (COPD). Repeated isolation of PPMs in bronchial secretions in stable patients was defined as colonisation; however, it is well documented that the presence of PPMs in the lower airways is associated with increased exacerbation frequency and severity, faster lung function decline and worse health status. Therefore, the term chronic bronchial infection (CBI) has been proposed to define this clinical situation.

    The presence of CBI in COPD is characterised by increased chronic inflammation not only in the airways and lung parenchyma, but also at a systemic level. Current evidence indicates that a significant amount of local and systemic inflammatory response in COPD may be attributable to the presence of PPMs. Since atherosclerosis is also characterised by chronic inflammation and oxidative stress, it has been hypothesised that CBI may be responsible for some extrapulmonary manifestations of COPD, particularly the high prevalence of cardiovascular comorbidities.

  9. Page 58
    Correspondence: A. Papi, Section of Respiratory Diseases, University of Ferrara, Via Savonarola 9, 44121, Ferrara, Italy. Email:

    A standardised definition of infective exacerbation of chronic obstructive pulmonary disease (COPD) still represents an unmet need in respiratory medicine because it relies on clinical empiricism with little evidence-based scientific support. Infective exacerbations of COPD are certainly clear events in the mind of practising physicians. However, there is little consensus on their definition and relevance of different infective aetiologies. Indeed, the efforts to assess the efficacy of new therapies in the treatment and prevention of COPD exacerbations have been hampered by the lack of a widely agreed and consistently used definition. There is a strong need for greater investment in research on infective exacerbations of COPD in order to promote a better understanding and clinical approach of this event in the natural history of COPD.

    Herein we will review the current concepts, definitions and aetiology of the infective exacerbations of COPD, underlining their strength and limitations.

  10. Page 68
    Correspondence: G.G.U. Rohde, Dept of Respiratory Medicine, Maastricht University Medical Center, P. Debyelaan 25, 6202AZ Maastricht, The Netherlands. Email:

    Respiratory viral infections belong to the most frequent infectious diseases. Small children in particular, but also elderly patients with underlying comorbidity such as chronic airways disease, are affected. The clinical course is often self-limiting but can be severe during exacerbations. There is a great diversity of respiratory viruses. This chapter introduces the most important respiratory viruses and comments on their specific role in chronic bronchitis and exacerbations of chronic obstructive pulmonary disease (COPD). Human rhinoviruses are most frequently detected in exacerbations of COPD. The inflammatory response of the airways to rhinoviruses leads to increased symptoms and exacerbations. Other important respiratory viruses include influenza, respiratory syncytial virus (RSV) and coronaviruses. In stable COPD, RSV seems to play a particular role, probably due to latent infection and effects on the underlying airways inflammation.

  11. Page 76
    Correspondence: S.L. Johnston, Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK. Email:

    Chronic obstructive pulmonary disease (COPD) is a disease characterised by acute exacerbations. Respiratory infections, including viruses and bacteria, are common aetiological agents and some studies have detected dual viral–bacterial infection during exacerbations. However, the mechanisms underlying virus–bacteria interactions in COPD are poorly characterised. In vitro studies have shown that viral infection can increase susceptibility to secondary bacterial infection, and animal models of sequential infection have revealed potential molecular mechanisms of how viral infection may impact upon subsequent secondary bacterial infection. A recently reported human experimental rhinovirus infection model of COPD exacerbation has provided additional evidence that viral–bacterial co-infection may be more common in COPD exacerbations than previously thought. Further understanding of the mechanisms involved in virus–bacteria interactions may facilitate development of novel therapies with the potential to reduce or prevent secondary bacterial infections following respiratory viral exacerbations in COPD. In this chapter, the evidence for dual viral and bacterial infection in COPD exacerbations is outlined, and existing evidence for underlying mechanistic interactions is discussed.

  12. Page 84
    Correspondence: F. Blasi, Dipartimento di Fisiopatologia e dei Trapianti, University of Milan, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, Italy. Email:

    Exacerbations represent an important event in the natural history of patients with chronic obstructive pulmonary disease (COPD). They are associated with considerable physiological deterioration and increased airway inflammatory changes, and may enhance disease progression by accelerating the decline in lung function. Some patients are prone to frequent exacerbations, which are an important cause of hospital admission and readmission, and these frequent episodes may have considerable impact on quality of life, activities of daily living and mortality. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype: the “frequent exacerbator”.

  13. Page 96
    Correspondence: G. Dimopoulos, Dept of Critical Care, University Hospital ATTIKON, 7 Kiprou Str, Athens 14569, Greece. Email:

    Chronic obstructive pulmonary disease (COPD) is frequently complicated by recurrent exacerbations. These are events in the natural course of the disease characterised by a change in the patient's baseline symptoms that is beyond day-to-day variations, is acute in onset and may require a change in regular medication. Exacerbations are mainly caused by respiratory infections of viral and bacterial aetiology. Since they are associated with high morbidity and mortality their treatment and prevention are important goals of the management of COPD. Antibiotics seem to have a beneficial effect especially in exacerbations with purulent sputum. Their use is mainly indicated in severe exacerbations that require hospitalisation, and for patients that have risk factors for poor outcome. The choice of the antibiotic is based upon the medical history, the local patterns of resistance and the severity of the underlying condition.

    Approved strategies for the prevention of exacerbations include smoking cessation and rehabilitation programmes, drug therapy and vaccination. Antibiotic prophylaxis has been a field of research. Macrolides and fluoroquinolones are currently being investigated with promising results. Until strong evidence becomes available, their use should be confined to selected patients, mainly in those with purulent expectorants.

  14. Page 107
    Correspondence: R. Wilson, Host Defence Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. Email:

    Bronchiectasis causes significant morbidity and mortality and is characterised by chronic airway inflammation and irreversible dilatation of bronchi. Pathogenesis varies depending on which of the aetiologies is responsible for the disease, and the clinical picture is heterogeneous for the same reason. In addition to conditions in which it is the primary diagnosis, bronchiectasis is associated with a number of diverse conditions such as rheumatoid arthritis and inflammatory bowel disease. Idiopathic bronchiectasis is the most common diagnosis, which emphasises our lack of knowledge about aetiology in many cases. The pattern of bronchiectasis in idiopathic cases tends to be bilateral, cylindrical and lower lobe predominant. Approximately one-third of cases occur post-infection. Severe infection of any sort can damage the bronchial wall sufficiently to cause bronchiectasis localised to the site of infection. Allergic bronchopulmonary aspergillosis, common variable immunodeficiency and primary ciliary dyskinesia are the next most common aetiologies. Non-tuberculous mycobacteria, particularly Mycobacterium avium complex, and aspiration are being increasingly recognised as causing bronchiectasis. Bronchiectasis may be present in obstructive airway diseases and, if chronic infection occurs, especially with Pseudomonas aeruginosa, it has a profound effect on the clinical course. Aetiology of bronchiectasis should be investigated because it may influence management.

  15. Page 120
    Correspondence: D. Bilton, Dept of Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. Email:

    Inhaled antibiotics are a useful tool in the management of chronic infection with Pseudomonas aeruginosa in the setting of cystic fibrosis (CF). Large randomised trials in CF have given us insight into the relationships between antimicrobial efficacy and clinical outcomes. The evidence base is now being expanded to non-CF bronchiectasis as new antibiotic formulations are developed and clinical trials performed. In the next few years we expect to see specific inhaled antibiotic preparations licenced for use in non-CF bronchiectasis. The challenges ahead are to identify the best regimens that produce the best efficacy whilst limiting production of antibiotic resistance.

  16. Page 127
    Correspondence: J. Rademacher, Dept of Respiratory Medicine, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Email:

    This chapter focuses on the prevention and treatment of exacerbations of non-cystic fibrosis (CF) bronchiectasis among adults. Due to a paucity of interventional randomised controlled trials the prevention and treatment of exacerbations is mostly empirical. However, patient education, physiotherapy and pharmacological airway clearance are the cornerstones of chronic management. In subjects with frequent exacerbations and chronic Gram-negative bacterial colonisations, inhaled antibiotics or anti-inflammatory macrolide long-term therapy should be considered, with the aim being to keep the number of exacerbations as low as possible. In acute exacerbations, empirical antibiotic therapy should be guided by the findings of previous sputum cultures, local epidemiology and patient factors, such as disease severity and (long-term) antibiotic pre-treatment, which determine the risk of infection by Pseudomonas aeruginosa or other difficult-to-treat or multidrug-resistant organisms. The majority of recommendations given in this chapter are based on comparatively small studies or expert opinions. Well-designed, randomised controlled trials in this field of respiratory medicine are urgently needed.