Bronchiectasis: The EMBARC Manual

© Springer International Publishing AG 2018

James Chalmers, Eva Polverino and Stefano Aliberti (eds.)Bronchiectasishttps://doi.org/10.1007/978-3-319-61452-6_1

1. Introduction

Robert Wilson¹, ²  

(1)

Host Defence Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK

(2)

Imperial College, London, SW7 2AZ, UK

Robert Wilson

Email: [email protected]

Bronchiectasis is a morphological term given to the lung condition when there is chronic dilatation of one or more bronchi. Professor Cayol in 1808 brought two specimens to the attention of the famous French physician René Laeanec, who then gave the first clinicopathological description of the disease in 1819 [1]. The term bronchiectasis was introduced later in 1846 by Swaine’s translation of Hasse’s book on diseases of the organs of circulation and respiration [2].

Until recently there was a generally held belief that bronchiectasis had ceased to be a significant problem in the developed world because improved living standards and the use of vaccines in childhood and antibiotics had reduced the prevalence of infections that caused the condition [3]. I had the honour to give the opening address this year at the first World Bronchiectasis Conference in Hanover. My talk was entitled ‘The Renaissance of Bronchiectasis’. This title was chosen because the opposite has occurred, so that whilst figures from different countries vary, there is general agreement that prevalence is increasing and that bronchiectasis becomes more common with older age [4–7]. Bronchiectasis is probably still underdiagnosed, partly because symptoms are indistinguishable from other ill-defined conditions such as chronic bronchitis and also because of the large number of bronchiectasis patients with a primary diagnosis of COPD or asthma [8, 9]. However, it is important to distinguish between clinical and radiological bronchiectasis. Airway dilatation can occur naturally as part of the ageing process, and in asthma dilatation, meeting radiological criteria for bronchiectasis can occur as part of airway remodelling without the clinical picture of cough, sputum and recurrent infections.

The reason for the increase in prevalence is probably multifactorial [10]. CT scans are now easily accessible and allow a radiological diagnosis, when previously another clinical diagnosis may have been made. Bronchiectasis is the final pathological pathway of a number of different causes, and some of these may be increasing such as nontuberculous mycobacteria. The population is ageing, and the increased prevalence of clinical bronchiectasis in older age may be ascribed to reduced host defences. Another cause of reduced host defences is the increased therapeutic use of immunosuppression, for example, in cancer and autoimmune disease.

The symptoms of bronchiectasis are a heavy burden and well recognised: chronic productive cough, recurrent chest infections, breathlessness (wheeze), haemoptysis and chest pains. I would draw particular attention to tiredness. Patients with poorly controlled disease are exhausted by the middle of the day when they have difficulty concentrating. When their condition improves with treatment, they report that they ‘have got their life back’. In addition to this considerable morbidity, needing frequent hospital visits and longer hospital stays than other chronic diseases, they also have reduced life expectancy [11–14]. About 20 years ago, we fully investigated a group of patients to validate the St George’s Respiratory Questionnaire (SGRQ) in bronchiectasis [15].When we looked back at the group after 13 years, about a third had died, 70% directly due to bronchiectasis. Age, SGRQ activity score, chronic Pseudomonas aeruginosa infection, airflow obstruction, lung restriction and impaired gas transfer were independently associated with mortality. CT features predicting mortality in multivariate analysis were increased wall thickness, a sign of inflammation and emphysema [12] and in a subsequent study average pulmonary artery diameter, a sign of raised pulmonary artery pressure [16]. Severity indices have been developed (BSI and FACED) which are calculated from easily obtained clinical data, and they can be used to predict risk of mortality, hospital admission and exacerbation [13, 14]. I believe these are very important measurements, and their application should now be explored in clinical practice and when enrolling patients into clinical trials.

When I started working for Professor Peter Cole in 1983, new patients came into our minimal dependency unit at Brompton for 48 h and underwent programmed investigations. We called this the ‘host defence workup’, and an advantage of the stay with us was several sessions of physiotherapy tuition. Although we now carry out the investigations as outpatients, the approach is unchanged, and this leads to diagnoses that alter management in about a quarter of cases: immune deficiency, allergic bronchopulmonary aspergillosis (ABPA), nontuberculous mycobacterial infection (NTM), inflammatory bowel disease, primary ciliary dyskinesia (PCD), atypical cystic fibrosis, rheumatoid arthritis, aspiration and partial obstruction of an airway [17].

Peter Cole and Rob Stockley proposed the vicious circle hypothesis [18] just before I joined the laboratory. This hypothesis consists of the following circle of events: impaired lung defences permit bacterial infection of the airway mucosa, which stimulates a neutrophilic inflammatory response that becomes chronic when it fails to eradicate the bacteria; the host inflammatory response causes tissue damage, e.g. via proteinase enzymes and reactive oxygen species which overwhelm the body’s ability to neutralise them; tissue damage further impairs the lung defences, allowing bacteria to persist; and so the circle continues and disease may progress and/or spread to a normal bystander lung. The entry point to the circle may differ depending on the aetiology. PCD and hypogammaglobulinaemia impair host defences; NTM is an infection directly causing bronchiectasis; ABPA and inflammatory bowel disease are inflammatory causes of bronchiectasis; and aspiration and smoke inhalation cause direct tissue damage. This hypothesis, ground-breaking when it was proposed, was supported by numerous in vivo and in vitro studies [19–21] and has remarkably stood the test of time so that today we still use it when considering pathophysiology of the disease. However, one weakness of the hypothesis is that it fails to explain why many patients are relatively stable for prolonged periods, whereas in others there is progression of disease.

Our thoughts about microbial pathogenesis also began to change. Instead of thinking about how bacteria invade and damage the host, we began investigating how bacteria evade the host defences and persist in the airway. The damage to the lung in these circumstances comes from the unsuccessful host inflammatory response. My own research was to characterise bacterial compounds which impair ciliary function [22]; other examples are biofilm mode of growth and the alginate gel of pseudomonas which both help the bacteria avoid phagocytes and the antigenic heterogeneity of non-typable Haemophilus influenzae which helps the bacterium avoid immune surveillance.

The striking result of all aetiology studies is the large proportion of patients that are idiopathic, usually about half of the cases. I wonder in 10 years’ time whether a number of new bronchiectasis aetiologies will have been discovered, and the idiopathic group will shrink, or whether we will find that the idiopathic group contains a large group of patients who have dysregulation of their inflammatory response to infection to explain why bronchiectasis occurs [23]. The proportion of idiopathic cases are influenced by how strictly the definition of postinfection bronchiectasis is made. I think it is difficult to diagnose a postinfection aetiology when a case presents in middle age reporting a historical illness in childhood, but many symptom-free years in between.

We found idiopathic cases, defined as no aetiology found in the ‘host defence workup’, to have predominately symmetrical lower lobe cylindrical bronchiectasis, they usually presented in early middle age, almost all had chronic rhinosinusitis (suggesting an abnormality throughout the respiratory tract) and symptoms were chronic from the outset. Whereas in postinfection bronchiectasis, defined as symptoms following a defined infection event, bronchiectasis was more unevenly distributed, they presented significantly younger, only about half had chronic rhinosinusitis and initially symptoms were often intermittent [18].

Persistent bacterial infection of the airway mucosa is a key event driving the vicious circle in most cases. Inflammatory bowel disease is the one aetiology in which patients with widespread bronchiectasis produce large volumes of purulent sputum which is often sterile on culture. H. influenzae is the most common pathogen, but it is management of P. aeruginosa which presents the greatest challenge. Patients presenting with pseudomonas infection usually have more severe and extensive bronchiectasis and more severe airflow obstruction [24]. It seems more likely that it is patients with severe disease that are susceptible to pseudomonas, rather than pseudomonas being the cause of their severe disease. However, once established, pseudomonas may be carried for life, and overall these patients have worse quality of life [25], increased risk of more rapid progression of disease [26] and reduced life expectancy [12].This is at least in part due to their more severe disease, but also difficulties in managing the infection mean airway inflammation is more difficult to control particularly when ciprofloxacin resistance occurs. The use of inhaled antibiotics, which take time to administer, side effects of frequent oral antibiotics and hospital admission for iv antibiotics all impair quality of life [15]. Management of pseudomonas infection is the area I would highlight as the one which we have most need for new approaches to treatment. There is also much debate about whether an attempt should be made to eradicate pseudomonas when it is first isolated and what that treatment should be [27]. In many cases eradication may appear to have been achieved at the end of treatment, but pseudomonas infection recurs with the next year; and other untreated patients will only culture pseudomonas intermittently. It is not known in either of these scenarios whether these are new strains or chronic infection. A randomised trial is urgently needed to determine whether attempted eradication after first isolation is a successful strategy.

A multidisciplinary team approach is essential in the management of bronchiectasis: physician, radiologist, immunologist, microbiologist, physiotherapist, clinical nurse specialist, dietician, psychologist (psychiatrist), social worker and occupational therapist. Good collaborations are also needed with ENT, thoracic surgery, cystic fibrosis (e.g. milder genotypes), gastroenterology (e.g. reflux, inflammatory bowel disease), rheumatology (e.g. rheumatoid arthritis, Sjogren’s syndrome) and a fertility clinic (e.g. primary ciliary dyskinesia, cystic fibrosis, Young’s syndrome). The heterogeneity of the bronchiectasis population is a major challenge, in terms of determining both their aetiology and also their presenting problem which may change over time, e.g. a postinfection case may develop ABPA or acquire a NTM infection. This is also a challenge when designing clinical trials, because treatments may not be equally effective in cases with different aetiologies and the severity of disease may affect response to treatment.

If an underlying cause for bronchiectasis has been discovered, e.g. hypogammaglobulinaemia, ABPA and NTM infection, then this should be addressed first. Treatment decisions in bronchiectasis are hampered by the lack of evidence from randomised trials, although thankfully this is beginning to change for long-term antibiotics. The lack of evidence is perhaps best illustrated by physiotherapy, which I have always regarded as the bedrock of bronchiectasis care, yet the best evidence to date comes from a single small crossover study which gave clear results favouring physiotherapy, particularly improvement in results of a cough questionnaire [28]. Treatments to improve mucus clearance are of great interest, and it was disappointing that mannitol failed to meet its primary endpoint [29], although there were sufficient positive results from the study to encourage more work in this area.

We live in a time when there is great concern about antibiotic resistance. Guidelines advise the use of antibiotics that are usually reserved as second line, e.g. co-amoxiclavulanate and quinolones, and that higher dosages and longer courses are used. This is understandable because the vicious circle hypothesis emphasises the importance of maximal bacterial suppression, recognising that eradication may not be possible. Investigation of the microbiome by molecular techniques will be particularly useful in understanding the effect of antibiotics in this regard. However, present guidelines increase the risk of resistance development, and the lack of sufficient evidence from trials to justify the guidelines weakens the argument for an aggressive antibiotic strategy. Clinicians managing bronchiectasis patients see the benefit of this strategy in individual cases, but more research is urgently needed.

The concentration of oral antibiotics reaching the airway mucosa is low, particularly for beta lactam antibiotics that penetrate cells and secretions poorly. This difficulty is increased due to scarring of the airway and excess secretions harbouring many millions of bacterial per millilitre. Inhaled antibiotics are therefore attractive, delivering high concentrations direct to the mucosa, although there may be difficulties of distribution due to mucus plugging and airway distortion. This approach should lessen the risk of resistance, although this needs to be carefully monitored.

Antibiotic prophylaxis has been recognised to improve bronchiectasis symptoms since the early study by the MRC [30]. However, to justify this approach, with the inevitable risks of side effects, particularly gastrointestinal, and antibiotic resistance, then a reduction in exacerbations should be demonstrated. This has not proved straightforward, even when high dosages of antibiotic are used [31]. More recent studies using inhaled antibiotics have shown significant reductions in bacterial numbers cultured from sputum and in exacerbation frequency [32–35]. The study by Howarth and colleagues was of particular interest because it showed benefits only in patients using the antibiotic regularly. It was a salutary lesson that even under clinical trial conditions, patients did not take the antibiotic as frequently as prescribed. This emphasises that it will not just be the potency of the antibiotic that is important but also its distribution in the bronchial tree; any side effects, e.g. cough and wheeze, that occur; and how easy/convenient the delivery machine is to use.

The vicious circle hypothesis emphasises the importance of controlling the inflammatory response. Physiotherapy achieves this by improving clearance of secretions containing bacteria and their products which attract neutrophils into the airway, antibiotics achieve it by killing bacteria, and a third approach is to reduce inflammation directly. Macrolide antibiotics have been shown in three randomised, placebo-controlled trials to reduce exacerbation frequency [36–38]. They are thought to do this by their anti-inflammatory rather than antibacterial properties. Other anti-inflammatory approaches, such as inhaled steroids, have been less successful [39], but this is an active area of research, e.g. neutrophil elastase inhibitors.

I have emphasised that more studies are needed to improve the evidence base for our investigation and management of bronchiectasis. For these to be successful, they must enrol a more homogeneous population. One approach has been to enrol patients for antibiotic trials by aetiology, e.g. idiopathic and postinfective [33, 35]. These cases are thought to have intact host defences, and their disease process is thought to be driven by bacterial infection. The success of this approach is dependent on the extent of investigations performed to define the aetiology. A second approach might be to define patient phenotypes as suggested by Alberti and colleagues [40]. These authors used cluster analysis of more than a thousand patients from European databases to define four groups that had different quality of life, exacerbation frequency and mortality: chronic pseudomonas infection, other chronic infection, daily sputum production and dry bronchiectasis. A third approach might base enrolment on different stages of the vicious circle hypothesis: mucus clearance, e.g. daily sputum volume above a certain level; type of bacterial infection, e.g. pseudomonas or non-pseudomonas; inflammation, e.g. a marker of inflammation such as free neutrophil elastase in sputum; and disease severity (lung damage), e.g. based on severity assessed by CT scan together with severity indices (BSI and FACED) [13, 14].

I am very excited that our current knowledge of bronchiectasis has been brought together in this textbook. Experts in each area will describe optimal medical management: how to investigate to exclude treatable causes, the best approaches to physiotherapy and the effectiveness of pulmonary rehabilitation, which antibiotics and what treatment regimens to best treat exacerbations, when to use antibiotic prophylaxis and the options available and who will benefit from anti-inflammatory approaches. In addition, which patients should we refer for consideration of surgery and transplantation, and when should we refer to allied disciplines? I am sure that an additional benefit will be that with this knowledge, the priorities for future research will become clearer. With the arrival of this book, the time for the renaissance of bronchiectasis truly feels to have arrived!

References

1.

Laennec RTH. In: Brosson JA, Chaude JS, editors. De L’Auscultation mediate ou traite de diagnostic des maladies des poumons et du coeur; Fonde; Principalement sur ce nouveau moyen d’exploration. Paris; 1819.

2.

Hasse CE. In: Swaine WE, editor. An original description of the disease of the organs of circulation and respiration. London: London Sydenham Society; 1846.

3.

Barker AF. Bronchiectasis. N Engl J Med. 2002;346:1383–93.CrossrefPubMed

4.

Chang AB, Grimwood K, Mulholland EK, Torzillo PJ. Bronchiectasis in indigenous children in remote Australian communities. Med J Austr. 2002;177:200–4.

5.

Wiss J, Metcaffe R, Edwards E, Byrres C. Arch Dis Child. 2005;90:737–40.Crossref

6.

Weycker D, Edelsberg J, Oster G, Tino G. Prevalence and economic burden of bronchiectasis. Clin Pulm Med. 2005;12:205–9.Crossref

7.

Quint JK, Millett ER, Joshi M, Navaratnam V, et al. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004–2013: a population-based cohort study. Eur Respir J. 2016;47:186–93.CrossrefPubMed

8.

Obrien C, Guest PJ, Hill SL, Stockley RA. Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care. Thorax. 2000;55:635–42.Crossref

9.

Patel IS, Vlahos I, Wilkinson TM, Lloyd-Owen SJ, et al. Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;170:400–7.CrossrefPubMed

10.

Goeminne C, De Soyza A. Bronchiectasis: how to be an orphan with many parents. Eur Respir J. 2016;47:10–3.CrossrefPubMed

11.

Onen ZP, Gulbay BE, Sen E, Yildiz OA, et al. Analyses of the factors related to mortality in patients with bronchiectasis. Respir Med. 2007;101:1390–7.CrossrefPubMed

12.

Loebinger MR, Wells AU, Hansell DM, Chiryanganya N, et al. Mortality in bronchiectasis: a long-term study assessing the factors influencing survival. Eur Respir J. 2009;34:843–9.CrossrefPubMed

13.

Chalmers JD, Goeminne P, Alberti S, McDonnell MJ. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med. 2014;189:576–85.CrossrefPubMedPubMedCentral

14.

Martinez-Garcia MA, de Gracia J, Monserrat VR, Giron R-M, et al. Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score. Eur Respir J. 2014;43:1357–67.CrossrefPubMed

15.

Wilson CB, Jones PW, O’Leary CJ, Cole PJ, Wilson R. Validation of the St George’s respiratory questionnaire in bronchiectasis. Am J Respir Crit Care Med. 1997;156:536–41.CrossrefPubMed

16.

Devaraj A, Wells AU, Meister MG, Loebinger MR, Wilson R, Hansell DM. Pulmonary hypertension in patients with bronchiectasis: prognostic significance of CT signs. Am J Roentgenol. 2011;196:1300–4.Crossref

17.

Cole PJ. A new look at the pathogenesis and management of persistent bronchial sepsis: a vicious circle hypothesis and its logical therapeutic connotations. In: Davies RJ, editor. Strategies for the management of chronic bronchial sepsis. Oxford: The Medicine Publishing Foundation; 1984. p. 1–20.

18.

Shoemark A, Ozerovitch L, Wilson R. Aetiology in adult patients with bronchiectasis. Respir Med. 2007;101:1163–70.CrossrefPubMed

19.

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;109:288–95.CrossrefPubMed

20.

Eiler J, Lapa Silva JR, Poulter LW, Lode H, Cole PJ. Cells and cytokines in chronic bronchial infection. Ann NY Acad Sc. 1994;725:331–45.Crossref

21.

Amitani R, Wilson R, Rutman A, Read R, et al. Effects of human neutrophil elastase and pseudomonas proteinases on human respiratory epithelium. Am J Respir Cell Mol Biol. 1991;4:26–32.CrossrefPubMed

22.

Wilson R, Pitt T, Taylor G, Watson D, et al. Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro. J Clin Invest. 1987;79:221–9.CrossrefPubMedPubMedCentral

23.

Boyton RB, Smith J, Ward R, Jones M, et al. HLA-C and killer cell immunoglobulin-like receptor genes in idiopathic bronchiectasis. Am J Respir Crit Care Med. 2006;173:327–33.CrossrefPubMed

24.

Miszkiel KA, Wells AU, Rubens MB, Cole PJ, Hansell DM. Effect of airway infection by Pseudomonas Aeruginosa: a computed tomographic study. Thorax. 1997;52:260–4.CrossrefPubMedPubMedCentral

25.

Wilson CB, Jones PW, O’Leary CJ, Hansell DM, Cole PJ, Wilson R. Effect of sputum bacteriology on the quality of life of patients with bronchiectasis. Eur Respir J. 1997;10:1754–60.CrossrefPubMed

26.

Evans SA, Turner SM, Bosch BJ, Hardy CC, Woodhead MA. Lung function in bronchiectasis: the influence of Pseudomonas Aeruginosa. Eur Respir J. 1996;9:1601–4.CrossrefPubMed

27.

White L, Mirrani G, Grover M, Rollason J, Malin A, Suntharalingam J. Outcomes of pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis. Respir Med. 2012;106:356–60.CrossrefPubMed

28.

Murray MP, Pentland JL, Hill AT. A randomised crossover trail of chest physiotherapy in non-cystic fibrosis bronchiectasis. Eur Respir J. 2009;34:1086–92.CrossrefPubMed

29.

Bilton D, Tino G, Barker AF, Chambers DC, et al. Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial. Thorax. 2014;69:1073–9.CrossrefPubMed

30.

Medical Research Council. Prolonged antibiotic treatment of severe bronchiectasis; a report by a subcommittee of the antibiotics clinical trials (non-tuberculous) committee of the MRC. Br Med J. 1957;2(5039):255–9.Crossref

31.

Currie DC, Garbett ND, Chan KL, Higgs E, et al. Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis. Q J Med. 1990;76:799–816.PubMed

32.

Murray MP, Govan JRW, Doherty CJ, Simpson J, et al. A randomised controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2011;183:491–9.CrossrefPubMed

33.

Wilson R, Welte T, Polverino E, De Soyza A, et al. Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study. Eur Respir J. 2013;41:1107–15.CrossrefPubMed

34.

Haworth CS, Foweraker JE, Wilkinson P, Kenyon RF, Bilton D. Inhaled colistin in patients with bronchiectasis and chronic Pseudomonas Aeruginosa infection. Am J Respir Crit Care Med. 2014;189:975–82.CrossrefPubMedPubMedCentral

35.

De Soyza A, Aksamit T, Bandel T-J, Criollo M, et al. Respire I: ciprofloxacin DPI 32.5 mg bd administered 14 day on/off or 28 day on/off vs placebo for 48 weeks in subjects with non-cystic fibrosis bronchiectasis. Eur Resp Soc. 2016;48:OA272. Abstract 272Crossref

36.

Wong C, Jauaram L, Karalus N, Eaton T, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet. 2012;380:660–7.CrossrefPubMed

37.

Altenburg J, Casper S, de Graaff MD, Stienstra Y, et al. Azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis. JAMA. 2013;309:1251–9.CrossrefPubMed

38.

Serisier DJ, Martin ML, MA MG, et al. Low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis. JAMA. 2013;309:1260–7.CrossrefPubMed

39.

Tsang KW, Tan KC, Hu PL, Ooi JC, et al. Inhaled fluticasone in bronchiectasis: a 12 month study. Thorax. 2005;60:239–43.CrossrefPubMedPubMedCentral

40.

Alberti S, Lonni S, Dore S, MJ MD, et al. Clinical phenotypes in adult patients with bronchiectasis. Eur Respir J. 2016;47:1113–22.Crossref

© Springer International Publishing AG 2018

James Chalmers, Eva Polverino and Stefano Aliberti (eds.)Bronchiectasishttps://doi.org/10.1007/978-3-319-61452-6_2

2. Imaging of Bronchiectasis

Mario Silva¹, Gianluca Milanese¹ and Nicola Sverzellati¹  

(1)

Section of Radiology, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy

Nicola Sverzellati

Email: [email protected]

2.1 Chest Radiography and Bronchography

Early-stage bronchiectasis is variably detectable depending on reader experience. Notably in this phase with subtle symptoms, the diagnosis is ideal because the therapy would be more beneficial. In case of severe bronchiectasis, radiographic signs are quite obvious, though inaccurate. Even in patients with symptoms of chronic bronchitis, the sensitivity of radiography is scant, namely, about 50% compared to bronchography [1].

Signs of bronchiectasis on chest radiography are usually depicted with more severe abnormalities. The signs of bronchiectasis include:

Linear markings radiating from the hila that reflect luminal dilation and variable bronchial wall thickening. This finding is also called tram track sign because the linear markings might run parallel to each other, resembling a railway (Fig. 2.1a). They may be the only finding in patients with cylindrical bronchiectasis, and moreover, it also may be seen with bronchial wall thickening in the absence of bronchiectasis. Therefore, the tram track sign is quite inaccurate.

Ring sign mirrors bronchial thickening when the major axis of bronchiectasis runs parallel to the radiation beam (Fig. 2.1a). Signet ring and tram track signs essentially reflect the same anatomic abnormality but in two different projective situations. Air-fluid level can be seen within the ring in case of abundant bronchial secretion.

Tubular or branching opacities reflect the mucus plugging within bronchial lumen (Fig. 2.1b), variably represented in different severity of bronchiectasis and different moments for the same patient [2].

Variation of pulmonary volume either reduction or increase can be seen in patients with bronchiectasis, according to the specific cause. Volume increase is associated with bronchiectasis in obstructive pulmonary disease. Conversely, asymmetric volume reduction with parenchymal opacification is associated with segmental or lobar atelectasis, which usually associates with fissural displacement and/or diaphragmatic obscuration. Volume reduction and reticular opacities are seen with restrictive pulmonary disease associated with fibrotic interstitial lung disease.

Vascular structures may be increased in size and may show fuzzy outline because of contiguous peribronchial inflammatory infiltrates and chronic fibrotic evolution.

Fig. 2.1

(a, b) Chest radiograph of a patient with bronchiectasis and its infectious acutization. (a) Chest radiographs show linear markings with parallel outline (arrow) and ring-like opacities (open arrow), reflecting bronchiectasis, respectively, perpendicular and parallel to the X-ray beam. (b) Chest radiograph shows linear/branching opacities (arrow) and nodular opacities (open arrow) with basal predominance during infectious acutization of bronchiectasis

Other signs such as pleural thickening, scarring, and formation of bulla can be variably seen as result of chronic inflammation and recurrent exacerbation.

Bronchography shows elegantly the abnormalities of bronchial outline as well as the paucity of bronchial divisions, and it can consistently differentiate cystic bronchiectasis from less severe degree of bronchial distortion. It was preferred over radiography for characterization of bronchial anatomy, until the widespread diffusion of high-resolution computed tomography (HRCT) [3].

2.2 Chest CT and HRCT

Computed tomography, notably HRCT, is the current reference standard for pulmonary imaging in the majority of respiratory diseases, including bronchiectasis. The technical requirements for dedicated imaging of the lung by HRCT are the following: thin-section acquisition (1 mm), high-spatial-frequency reconstruction, and appropriate window setting. These are the paramount technical features for accurate characterization of bronchial wall distortion and, in particular, thickening, which might be otherwise overrated. Notably, thicker section, low-spatial-frequency reconstruction, and overly narrow (<1000 HU) or high (> −250 HU) window settings would render blurred interface between the bronchial wall (internal and external aspects) and surrounding air, resulting in artificial bronchial wall thickening [4]. Volumetric acquisition allows the utmost confidence in diagnosis of bronchiectasis [5]. Conversely, serial CT suffers from possible overlooking areas of focal bronchiectasis, located exclusively in areas skipped by interspacing between slices. On serial acquisition, bronchiectasis might be referred as cystic lesions, and vice versa, because the gap between slices does not allow to assess the continuity of bronchial structures. On the other hand, volumetric display and multiplanar reconstruction increase confidence in the differential between bronchiectasis and a range of reticular and cystic abnormalities, in particular honeycombing. Volumetric acquisition renders the volumetric characteristics of tubular (e.g., bronchi) or rounded isolated (e.g., cysts) structures. Of note, cystic bronchiectasis may be misinterpreted as cyst if the bronchus between subsequent cystic enlargements is near normal, despite volumetric acquisition.

Small cylindrical bronchiectasis in a single pulmonary segment appears in a significant percentage of the healthy population; therefore, they should not be considered [6]. However, the definition of minor positive finding for bronchiectasis is subject of debate, notably in association with the underlying chronic clinical condition. For instance, the definition of minor bronchiectasis in a chronic obstructive pulmonary disease (COPD) population was represented by slightly dilated or non-tapering airways that involved less than four segments [7]. In patients with emphysema, minimal bronchiectasis was defined by involvement of one bronchopulmonary segment or even part of it [8]. A comprehensive description of bronchiectasis in different clinical scenarios was provided by Tan et al. who reported the following specific prevalences: 19.9% in normal never smoker without respiratory symptoms, 19.9% in smokers, 14.1% in patients with mild COPD, 22% in patients with moderate COPD, and 35.1% in patients with severe or very severe COPD [9]. They used the definition of bronchiectasis related to the mild increase in the bronchial–arterial ratio and argued this method could be overly sensitive. The bronchial–arterial ratio is particularly good to provide a standardized metric. However, the ratio could be overrated from pathologies involving the artery, as it was demonstrated in COPD. Diaz et al. reported that the majority of cases of increased bronchial–arterial ratio in COPD patients were related to a reduced size of the blood vessel [10]. The same group suggested that such ratio might be inappropriate even in healthy never smokers [11]. Therefore, there is no consensus on the definition of the minimal HRCT finding that should be deemed disease per se. In clinical practice, the integration with complete clinical history would allow an optimal accuracy in reporting HRCT findings.

The major anatomic detail of HRCT comes with the relevant concern of significantly increased radiation exposure that should be balanced with the clinical advantage of such imaging method, especially in case of young and female patients. Low-dose HRCT should be considered in selected cases. Clinical low-dose technique (≈6 months of background exposure) can reduce the radiation exposure by about five times compared to standard HRCT (≈2 years of background exposure), namely, to the equivalent of about 15–20 chest radiographies (≈10 days of background exposure) [12].

Follow-up of bronchiectasis is not recommended by HRCT, yet bronchiectasis evolution was described in association with low BMI and infection from Pseudomonas aeruginosa [13]. Side-by-side comparison between baseline and follow-up scan might be the optimal review layout to assess bronchiectasis evolution with minimal methodological bias [14].

HRCT semiology of bronchiectasis includes both direct and indirect signs. Direct signs of bronchiectasis reflect morphological abnormalities of the bronchial wall, namely:

Bronchial dilatation: minor cylindrical dilation is usually seen as absence of normal tapering (Fig. 2.2a). This is best depicted in airways that run parallel to the axial plane, such as lower segments of upper lobes and middle lobe. In case of bronchial dilation, the ratio between the diameters of bronchial lumen and its homologous pulmonary artery exceeds 1 [15]. The disproportion between bronchus and artery recalls the signet ring appearance in lower lobes and apical segment of upper lobes, where the bronchovascular bundle runs perpendicular to the axial plane. Minor bronchiectasis can also be detected when airways are visible within 1 cm of costal pleura [16]. Varicose and cystic bronchiectasis are quite obvious on HRCT [17] (Fig. 2.2b, c). The former is characterized by a beaded appearance, whereas the latter is seen as thin-walled cystic spaces variably associated with fluid levels. In cystic bronchiectasis, the accompanying pulmonary artery can be obliterated; thus, the differential might be challenging with bullous emphysema and cystic lung diseases. Expiratory scan can be used for the differential because bronchiectasis tends to collapse, whereas other cystic abnormalities do not [18].

Fig. 2.2

(a–c) Bronchiectasis characterized by computed tomography into the three main morphological types. (a) Cylindrical bronchiectasis on CT is seen as non-tapering of bronchial lumen (arrows). (b) Varicose bronchiectasis characterized by luminal enlargement (arrow) with interposed stenosis (open arrow). (c) Cystic bronchiectasis characterized by balloon-like dilatation of the bronchial lumen (arrow) and air–fluid levels from mucus deposition (open arrow)

Bronchiectasis associated with fibrotic interstitial lung disease is usually referred as traction bronchiectasis. By definition, they are non-tapering airways surrounded by abnormal lung parenchyma such as ground-glass and/or reticular opacity. Therefore, the term traction bronchiectasis should be utilized only in lung fibrosis. Their predominant distribution depends on the underlying subtype of lung fibrosis (e.g., basal predominance in usual interstitial pneumonia, upper lobes predominance in sarcoidosis). Traction bronchiectasis may also vary in severity, which has a strong prognostic value.

Bronchial wall thickening: this sign is variably seen, and it is possibly reversible because it likely reflects the specific inflammatory status of a bronchial portion in a specific moment. Standard definition of bronchial thickening on CT is not obvious. In case of mild bronchiectasis, bronchial thickening can be defined when the luminal diameter is <80% of external diameter [19]. However, this definition is not suitable for larger bronchiectasis. In a study about COPD-related bronchiectasis, the bronchial wall thickness (graded on a qualitative 5-point scale) was significantly associated with severity of bronchiectasis [7].

Airway plugging: focal opacities or also elongated finger-in-glove opacification of bronchial lumen can be seen in bronchiectasis; this reflects the mucoid impaction at any bronchial generation, notably in the central airway. Mucus impaction can appear also as Y- or V-shaped opacities that reflect thickening of the bronchial wall. Centrilobular nodules (both solid and subsolid) attached to fine Y- or V-shaped opacities represent the so-called tree-in-bud pattern that reflects exudative filling in small airway and airspace [20]. It is important to differentiate between peripheral mucus plugging and central mucoid impaction, because the latter is specific for allergic bronchopulmonary aspergillosis (ABPA).

Diffuse or localized parenchymal abnormalities can be associated with bronchiectasis, reflecting abnormalities in the airspace, such as:

Mosaic attenuation pattern: areas of decreased attenuation that have been attribute to obstruction from obliterative bronchiolitis. Vascular paucity (reduction in number and caliper of vessels) is a key finding for differential of subtle mosaic appearance and could be attributed to hypoxic vasoconstriction in areas with poor ventilation [21]. Mosaic attenuation is mostly associated with overt bronchiectasis, but it can also be seen as isolated CT finding. Expiratory scan enhances the density gradient between areas of air trapping and the normal lung (Fig. 2.4c), which allows differential with panlobular emphysema [22].

Volume loss: volume loss with consolidation can be the consequence of chronic inflammation from bronchiectasis and consequent peribronchial fibrosis. In this case, airways appear exceptionally crowded within parenchymal collapse. Conversely, volume loss is the cause of bronchiectasis, namely, traction bronchiectasis, in fibrotic interstitial diseases. Parenchymal reticulation and vascular or fissural distortion are hallmark of traction bronchiectasis that yield specific prognostic value.

Thickening of interlobular septa: this sign was found more frequently in lobes with bronchiectasis compared with lobes without bronchiectasis, in a cohort of patients with idiopathic bronchiectasis. Allegedly, the prominent inflammatory infiltration into the submucosa of bronchiectasis might lead to lymphatic congestion and, thus, thickening of the interlobular septa [23]. Noteworthy, interlobular and intralobular thickening is also seen in fibrotic interstitial diseases with traction bronchiectasis, again to be differentiated from other forms of bronchiectasis.

Bronchiectasis can associate with hemoptysis. Bronchiectatic hemoptysis ranges from minor sporadic event to major life-threatening hemorrhage. Hemorrhage is more frequently derived from systemic bronchial or non-bronchial arteries, while it is sporadically caused by pulmonary arteries [24]. Angiographic CT with intravenous injection of contrast agent plays a major role in imaging the mediastinum, notably the vascularization of bronchiectasis from systemic or pulmonary arteries (Fig. 2.3) [25]. Angiographic CT has even higher yield than conventional angiography because it provides better depiction and traceability of the bronchial arteries [26]. Angiographic CT is used for specific detection of arteries causing hemoptysis with the aim of planning endovascular treatment [27].

Fig. 2.3

Angiographic CT of the chest in coronal reconstruction of a patient with recurrent severe hemoptysis. The opacification of bronchial arteries (see origin from descending aorta) shows the vascular enlargement that cause recurrent hemoptysis

2.3 Magnetic Resonance Imaging

Lung imaging by magnetic resonance (MR) has been long investigated, and efforts are conspicuous especially in pediatric population to avoid radiation exposure.

MRI has significantly longer times of acquisition and limited spatial resolution compared to HRCT. Motion artifacts (e.g., cardiac pulse, respiratory movement of diaphragm) are among the limitations of MRI in the chest. Of note, the main limitation of MR in imaging the lung derives from low concentration of hydrogen (the atom that provides the MR signal) and abundance of oxygen (an atom that causes noise). However, bronchiectasis is typically characterized by increased density of lung structure; therefore, MR found its indication in specific cases of bronchiectasis. In particular, MR is used in pediatric patients with cystic fibrosis because the significant chronic wall thickening and abundance of mucus bring more resonance substrate in the pulmonary volume. In these patients, MR is mandatory because the radiation exposure from HRCT would significantly increase the risk of radio-induced malignancy. The potential advantage of MR lays in the possibility to provide more than morphological information about the bronchial wall. However, MR is still quite far from clinical applicability for the assessment of bronchiectasis in adulthood.

2.4 Etiology of Bronchiectasis and Typical Radiological Findings

Ancillary CT signs can suggest the etiology of bronchiectasis in less than half of patients. Typical CT features of one etiology can be seen, without being exclusive. Idiopathic bronchiectasis is more common in lower lobes [28]. However, the differential between idiopathic bronchiectasis and bronchiectasis associated with other cause is usually left to clinical integration because radiologic features are not accurate for this purpose. Thereafter, typical CT features of different bronchiectasis etiologies are reported, which could be used to pitch differential diagnosis (Table 2.1).

Table 2.1

Summary of cause of false-negative or false-positive finding for diagnosis of bronchiectasis on HRCT

2.4.1 Allergic Bronchopulmonary Aspergillosis (ABPA)

Bronchiectasis in ABPA is predominantly apical and centrally located. Typically, segmental and subsegmental bronchi are enlarged and filled with dense mucus that represents the chronic airway colonization from Aspergillus fumigatus with deposition of calcium salts (expectoration of brown plugs can be referred). ABPA should be suspected in asthma and cystic fibrosis, albeit plugging is not exclusive of aspergillus colonization (skin test should be prompted in these scenarios). Central plugs resemble a glove finger (finger-in-glove sign) (Fig. 2.4) and are variably associated with small airway filling revealed by tree-in-bud opacities. Chronic inflammation may be associated with lymph node enlargement and calcification, which can also occur in chronic granulomatous or professional diseases (e.g., tuberculosis, sarcoidosis, silicosis, etc.).

Fig. 2.4

(a–c) Mucus impaction in allergic bronchopulmonary aspergillosis (ABPA). (a) Large tubular intrabronchial opacity (arrow) in anterior segmental bronchus of the left upper lobe, which reflects central mucus impaction in ABPA. It can also be called finger-in-glove sign according to the resemblance with glove finger. (b) Mediastinal window shows the high density of the mucus impaction (arrow), an ancillary sign of ABPA. (c) Expiratory acquisition enhances mosaic attenuation of lung parenchyma, which is caused by air trapping. It is seen as triangular darker areas of the lung

2.4.2 Nontuberculous Mycobacterial Infection

Bronchiectasis in nontuberculous mycobacterial infection is usually minor and oligosymptomatic at early stage. Typically, but not exclusively, bronchiectasis occur in the middle lobe and lingula (this distribution is also known under the name Lady Windermere syndrome, derived from Oscar Wilde comedy), and they are associated with nodular component that reflects exudative process in small airway and airspace, namely, the tree-in-bud pattern (Fig. 2.5). Bronchial nontuberculous mycobacteriosis is associated with colonization from Mycobacterium avium complex (MAC) [29]. The early diagnosis is quite challenging because of the unspecific clinical presentation; radiology is useful in depicting minor bronchiectasis and its slow progression. Among signs of progression, severity of bronchiectasis and associated atelectasis should be always carefully interpreted. Mosaic perfusion on inspiratory scan is a common finding, which is characterized as air trapping on expiratory scan.

Fig. 2.5

(a–c) Slow temporal evolution of peripheral mucus plugging in nontuberculous mycobacteriosis from Mycobacterium avium complex (MAC). (a) Year 2008, small nodular intrabronchial opacities (arrow) are seen in the right middle lobe and lingula, along with minor bronchiectasis. (b)