Paediatric Respiratory Reviews 12 (2011) 104–110

Mini-Symposium: Non-CF Bronchiectasis

Pathogenesis of bronchiectasis§

Paul King *

Department of Respiratory and Sleep Medicine and Monash University Department of Medicine, Monash Medical Centre, Melbourne, Australia

A R T I C L E I N F O

Keywords:

Non-CF Bronchiectasis

pathophysiology

host defences

immunology

microbiology

S U M M A R Y

Non-cystic fibrosis bronchiectasis is a heterogeneous condition and its pathogenesis is still not well

defined. A combination of a defect in host defense and bacterial infection allows microbial colonization

of the airways resulting in chronic inflammation and lung damage. An ongoing cycle of infection and

inflammation may be established. Typically, the walls of the small airway are infiltrated by inflammatory

cells causing obstruction whilst mediators, such as proteases released predominantly by neutrophils,

damage the large airways resulting in bronchial dilatation. Adjacent parenchyma is also involved in the

inflammation. Lung function testing generally demonstrates mild to moderate airflow obstruction that

progresses over time. There are a large number of different aetiologic factors associated with

bronchiectasis. A variety of different microbial pathogens is involved and they change as disease

progresses.

� 2010 Elsevier Ltd. All rights reserved.

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Paediatric Respiratory Reviews

INTRODUCTION

Bronchiectasis remains a common and important cause ofrespiratory disease and is defined by the presence of permanentand abnormally dilated bronchi. It is usually diagnosed by highresolution computed tomography scanning (HRCT). In very youngchildren it may not be possible to use HRCT and patients may beclassified as having clinical bronchiectasis. This article will focus onnon-cystic fibrosis (CF) bronchiectasis.

Bronchiectasis arises from chronic airway inflammation that isdriven by persistent infection. The main clinical manifestation is aproductive cough. The pathogenesis of this condition is complexand still not well defined with a range of different factors thatresult in chronic airway damage. This review will discuss a varietyof areas which give insights into the pathogenesis of this condition.

CYSTIC FIBROSIS/NON-CF BRONCHIECTASIS

A primary manifestation of cystic fibrosis is bronchiectasis.There is still some controversy about the differentiation betweencystic fibrosis and non-CF bronchiectasis.

Cystic fibrosis arises from a defect in the cystic fibrosistransmembrane regulator (CFTR) which functions as a chloridechannel in epithelium (present in the lung, gastro-intestinal tract(GIT) and skin). Deficiency of the CFTR is thought to be associated

§ The author has no conflict of interest in the publication of this work.* Respiratory and Sleep Medicine, Monash Medical Centre, 246 Clayton Rd,

Clayton, Melbourne, 3168, Australia. Tel.: +61 3 9594 6666; fax: +61 3 9594 6415.

E-mail address: paul.king@monash.edu.

1526-0542/$ – see front matter � 2010 Elsevier Ltd. All rights reserved.

doi:10.1016/j.prrv.2010.10.011

with abnormal chloride transport that probably predisposes todehydrated mucous and leads to failure of mucociliary clearance.

CF occurs in homozygotes. The incidence of heterozygosity inCaucasian populations is approximately 1/25 (but is much lower inother ethnic groups). There are over a 1000 different mutations ofthe CFTR channels. It has been suggested that 1), a diagnosis of CFmay be missed due to failure to screen for all the relevantmutations and 2), the presence of 1 gene mutation (i.e.heterozygosity) may be associated with an increased risk ofbronchiectasis (possibly arising from decreased CFTR proteinproduct that impairs host defense)1,2. A variety of studies arereported in the literature3–6.

All Caucasian children with bronchiectasis should ideally bescreened for bronchiectasis (sweat test and relevant mutationanalysis) and if they have specific features (e.g. GIT manifestationsor family history) more thorough investigation could be con-sidered. Currently, the great majority of patients who present withbronchiectasis probably do not have cystic fibrosis.

PREVALENCE AND EPIDEMIOLOGY

The prevalence of bronchiectasis has not been well defined andprobably varies significantly between different populations. It wasthought that the introduction of antibiotics would effectively curebronchiectasis and this has led to a low index of suspicion withconsequent underdiagnosis. The advent of HRCT has made thediagnosis much easier and it has become apparent that bronch-iectasis remains a major cause of respiratory disease.

Weyeker et al have estimated that there are at least 110 000adults with bronchiectasis in the United States7. Studies describe ahigh prevalence of bronchiectasis in certain indigenous popula-

P. King / Paediatric Respiratory Reviews 12 (2011) 104–110 105

tions including Australian aborigines8, New Zealand Maoris9 andAlaskan natives10.

Bronchiectasis is also thought to be common in developingnations but this has not been clearly documented yet in theliterature. Tsang et al report an incidence of 16.4 per 100 000 inHong Kong which is likely to be an underestimate11.

Sex and age may also have a role in the pathogenesis ofbronchiectasis. Bronchiectasis is more common in women; thereason for this is not clear. Most studies have reported that patientsfirst developed symptoms in childhood. This may reflect therelative immaturity of immune function.

LOCALIZED/GENERALIZED DISEASE

Bronchiectasis may be arbitrarily classified into localized (onelobe) or generalized disease (multilobar). It may also only involvethe lower respiratory tract or it may be accompanied by upperrespiratory tract disease.

Localized disease usually appears to arise in the context ofbronchial obstruction. This obstruction may be from a slow-growing tumour or inhaled foreign body. On a world-wide basisprobably the most common form is in the context of amycobacterial infection. This has been previously described by[()TD$FIG]

Figure 1. CT findings in patients with bronchiectasis: A) Shows localized cystic left upp

emphysema in association with bronchiectasis. C) Demonstrates pansinusitis in a subj

Whitwell12. Mycobacterial infections may result in prominentperibronchial lymphadenopathy in an infected lobe. This lymphnode enlargement results in localized obstruction and partialcollapse of an infected bronchus with secondary airway inflam-mation. When the lymph nodes decrease in size the obstruction isrelieved but there is resultant bronchiectasis.

Most cases of bronchiectasis present with generalized disease.In addition the majority of patients with childhood-onset diseasehave prominent upper respiratory tract symptoms as well13.Whether the inflammation is 1), localized and spreads or 2), startsoff as a generalized abnormality is not known. In the author’sexperience subjects with childhood onset disease generallydescribe simultaneous onset of upper and lower respiratory tractsymptoms (Figure 1A).

PATHOPHYSIOLOGY OF BRONCHIECTASIS

Bronchiectasis is characterized by intense airway inflammationwhich arises from infection with microorganisms predominantlybacteria. There are no animal models of bronchiectasis nor arethere studies of the early pathologic changes in this condition. Assuch the pathophysiology of this condition is still not well defined.

er lobe bronchiectasis occurring after mycobacterial infection. B) Shows localized

ect with childhood onset bronchiectasis.

Table 1Important pathology findings in bronchiectasis

Reid’s classification of bronchial dilatation

Tubular

Varicose

Cystic

Whitwell’s classification of bronchiectasis subtypes

Follicular

Saccular

Atelectatic

Infiltration of the bronchial wall with a cellular infiltrate of lymphocytes and

macrophages to cause obstruction of the small airways

Neutrophils produce mediators such as proteases which damage the larger airways

to cause dilatation

Spread of inflammation from bronchi to cause adjacent parenchymal inflammation

P. King / Paediatric Respiratory Reviews 12 (2011) 104–110106

The most well recognized model of the development ofbronchiectasis is the ‘‘Vicious cycle hypothesis’’ described byCole14. He proposed that there was an initial event (e.g. a viralinfection) that compromised mucociliary clearance and allowedinfection of the respiratory tract. The infectious pathogens causedinflammation with further impairment of mucociliary functionwhich resulted in bacterial proliferation and more inflammation.Thus a self-perpetuating cycle was established that led toprogressive lung damage. The primary emphasis in this modelwas on the role of mucociliary clearance but recently a broaderapproach has been taken. Any cause of immune dysfunction canpotentially allow the establishment of respiratory tract infectionwhich may then lead to progressive damage.

The pathophysiology can also be considered in terms of 1),effects of bacterial pathogens on the lung and 2), responses of hostcells to these pathogens.

Effects of bacterial pathogens on lung

The best described effect of bacteria is on mucociliaryclearance15. Common bacterium including Haemophilus influenzae,Streptococcus pneumoniae and Pseudomonas aeruginosa releasemediators which can inhibit ciliary function and directly damageciliated epithelium. They may also inhibit mucous function.

H. influenzae can stimulate mucous production and directlydamage the airway epithelium. It has been shown that thisbacterium may adhere and invade into respiratory epithelial cellsand into the interstitial tissue of the submucosa16.

The bacteria may release products such as glycoproteins andstimulate release of chemokines such as interleukin-8 (IL-8) whichattract large numbers of neutrophils to the site of inflammation inbronchiectasis.

P. aeruginosa (and possibly H. influenzae) has the ability tosecrete biofilms which form an impermeable matrix around thebacteria17. These biofilms protect the bacteria from the actions ofimmune cells and antibiotics and are associated with severedamage to the underlying airway.

Response of host cells to pathogens

Neutrophils are the main cell in the sputum and bronchoal-veolar lavage (BAL) of subjects with bronchiectasis18. They are alsofound in high densities in the lamina propria of bronchial mucosa.Activated neutrophils produce a variety of mediators such aselastase, metalloproteinases and reactive oxygen species19. Thesemediators digest airway elastin, basement membrane collagen andproteoglycan and have a major role in weakening the bronchialwall and resultant bronchial dilation. Elastase produced byneutrophils may also damage epithelial cells and cause gobletcell hyperplasia and mucous hypersecretion.

The bronchial wall is infiltrated by macrophages and lympho-cytes18,20. The macrophages contribute to neutrophil influx andalso release proteases. Lymphocytes are associated with increasedlevels of immunoglobulin production and immune complexes.

It has been reported that other cells such as eosinophils (insmall numbers) and epithelial cells may contribute to theinflammation in bronchiectasis.

PATHOLOGY

Pathology studies in bronchiectasis have demonstrated that thekey features are dilatation of the subsegmental airways which areinflamed, tortuous and obstructed by secretions. Bronchioles areinvolved in the inflammatory process and there may be fibrosis.There is also usually parenchymal lung damage. Pulmonaryarteries may thrombose and recanalize but the vascular supply

arises predominantly from hypertrophied bronchial arteries. Reiddescribed 3 main subtypes of bronchiectasis; 1) tubular in whichthere was smooth dilatation of the bronchi 2), varicose wheredilated bronchi had regular indentations and 3), cystic in which thebronchi ended in blind sacs21.

Perhaps the best study on the pathology of bronchiectasis wasperformed by Whitwell who studied 200 consecutive lungresection specimens12. He demonstrated that bronchial wall wasinfiltrated with inflammatory cells. There was loss of elastin and inmore severe cases loss of cartilage and muscle which wasassociated with bronchial dilatation. Whitwell described 3different subtypes 1), follicular 2), saccular and 3), atelectatic(as described previously in the context of mycobacterial infection).

The follicular subtype was the dominant form and thiscorresponds to tubular bronchiectasis (the main form currentlydiagnosed using HRCT). The dominant feature of this form was anextensive inflammatory infiltrate in the bronchial wall of the smallairways which formed lymphoid follicles and was associated withobstruction of the small airways. In contrast the larger airwayswere dilated with loss of elastin, cartilage and muscle. Interstitialpneumonia was present in the parenchyma adjacent to theaffected bronchi and ranged in severity from mild to solidifiedlung.

More recently studies have demonstrated the predominantinfiltrate in the bronchial wall is composed of T lymphocytes andmacrophages whilst the main cell in the bronchial lumen is theneutrophil (which produces proteases and other mediators) todamage the bronchial wall.

A radiologic study has described a high prevalence ofemphysema adjacent to areas of bronchiectasis consistent withWhitwell’s observation that inflammation spreads out into theadjacent parenchyma22. Localized emphysema in association withbronchiectasis is demonstrated in Figure 1B.

The studies of the pathology of bronchiectasis have demon-strated that there is progressive inflammation predominantly inthe small airways that causes damage to the larger airways withbronchial dilatation (the key feature of bronchiectasis) andadjacent parenchymal infiltration. Important pathology findingsin bronchiectasis are summarized in Table 1.

LUNG FUNCTION

Patients with bronchiectasis usually have mild to moderateairflow obstruction and over-time develop progressively worsen-ing airflow obstruction23–25. This may be surprising as the cardinalfeature of bronchiectasis is airway dilatation. This paradox can beexplained by the pathology findings from Whitwell’s study whichdemonstrated that whilst the large airways were dilated the smallairways were obstructed; as most of the pulmonary tree iscomposed of small airways the net effect is obstruction. A similareffect has also been demonstrated a more recent study which

Table 2Lung function in bronchiectasis

Most common pattern is mild/moderate airflow obstruction

Decline in lung function (1-2% decrease in FEV1 per year)

Decline in lung diffusing capacity

High incidence of airway hyper-reactivity

FEV1 = forced expiratory volume in 1 second.

P. King / Paediatric Respiratory Reviews 12 (2011) 104–110 107

showed small airway constrictive bronchiolitis as manifest as amosaic pattern on CT was the primary feature associated withairflow obstruction26.

Parenchymal lung involvement is a prominent feature ofbronchiectasis. As such the lung diffusing capacity may be affected.A recent study has described a progressive decline in lung diffusingcapacity in a cohort of subjects followed up for 8 years27. This isconsistent with the spread of inflammation out into the adjacentparenchyma with consequent mild impairment of gas exchange.

Another prominent finding in bronchiectasis is the presence ofbronchial hyper-reactivity. Studies have demonstrated that airwayreversibility is present in up to 40% of patient cohorts28,29. Twoother groups have demonstrated a positive histamine challenge(i.e. > than 20% decline in FEV1) in 30-69% of patients30,31.Whether this airway reactivity suggests that there is a high degreeof asthma in these subjects has not been clearly determined. Thestudies of cell types and mediators from bronchiectasis are notconsistent with a typical asthma inflammatory phenotype. Theairway hyperresponsiveness may be a manifestation of airwayinflammation arising from infection. Lung function manifestationsare summarized in Table 2.

SPECIFIC CAUSES OF BRONCHIECTASIS

There are a large number of aetiologic factors that have beendescribed to cause bronchiectasis. As there is generally a very longhistory before a definitive radiological diagnosis of bronchiectasisit may be difficult to be certain of the exact role of such factors inthe pathogenesis of bronchiectasis. There also may be multiplefactors in the same patient. It may be more appropriate to considerthem as risk factors (e.g. as in risk factors for hypertension orischaemic heart disease) rather than as a single predominantcause. Important causes are listed in Table 3.

Table 3Important causes of bronchiectasis

Post-infectious

Pneumonia, measles, whooping cough

Viral infection

Mycobacterial infection

Mucociliary disorders

Primary; primary ciliary dyskinesia

Secondary

Obstruction

Foreign body, tumour, mycobacterial infection

Immune dysfunction

Specific immune deficiencies; hypogammaglobinaemia, HIV, MHC-I deficiency,

TAP-1 deficiency, IFN- g receptor deficiency

Allergic bronchopulmonary aspergillosis

Malnutrition/social disadvantage

Extremes of age

Rheumatic inflammatory conditions

Rheumatoid arthritis, inflammatory bowel disease

Miscellaneous

Willliams Campbell syndrome

Alpha 1-antitrypsin deficiency

Chronic obstructive pulmonary disease/smoking

Aspiration

HIV = human immunodeficiency virus, MHC-I = major histocompatibility complex

class I, TAP-1 = transporter associated protein, IFN-g = interferon gamma

Post-infectious

The most commonly attributed cause of bronchiectasis ischildhood infection. This has been described particularly followingpneumonia, measles and whooping cough. There are some factorswhich complicate the causation of bronchiectasis after infection.Generally theses studies have used long-term retrospective recallto diagnose post-infectious disease. Bronchiectasis is characterizedby recurrent exacerbations which occur as part of the conditionThe infections that have been most commonly associated withbronchiectasis are extremely common with the seroprevalence ofmeasles being > than 90% and whooping cough > 50%32 inunvaccinated adults. A study of the effect of whooping cough andchildhood pneumonia on a cohort of 1392 British adults found aslight decrease in lung function but no subject was recorded tohave bronchiectasis33. A key factor in the pathogenesis ofbronchiectasis is the establishment of chronic infection of theairways but this appears to be distinct from the entity of post-infectious bronchiectasis described in the literature.

Infection in early childhood may cause structural damage to thelung particularly the epithelium and predispose to secondaryinfection. This has been anecdotally described to occur after viralinfection although this has been hard to prove. Beecroft describedbronchiectasis occurring in small children following an adenovirusoutbreak34. As described previously mycobacterial infection maycause bronchiectasis by bronchial obstruction and this may be avery important cause in developing countries. In indigenouspopulation such as Australian aborigines recurrent severe andundertreated infections in childhood may well cause significantlung damage and secondary bronchiectasis.

Mucociliary clearance

The mucociliary apparatus is a first line structural defenseagainst pathogenic microorganisms. There have been several wellrecognized conditions that impair its function. The best describedexample is cystic fibrosis. In addition to lower respiratory tractdisease patients nearly always have severe upper respiratory tractdisease as well. Infertility is also an important manifestation.

Primary ciliary dyskinesia (PCD) is characterized by lack ofciliary function that contributes to retention of secretions andrecurrent infections. The defect is due to an absence of the dyeninarm protein which prevents co-ordinated movement of the cilia.PCD is autosomal recessive with an incidence of 1 in 15 000 to 40000 births. About half of the patients with this condition will havesitus inversus (Kartegener’s syndrome)35.

Young’s syndrome has been characterized by normal ciliaryfunction but abnormal tenacious mucous. This condition is rareand there is some dispute as to whether it is a distinct entity.

There may also be secondary impairment of mucociliaryfunction in association with bacterial infection as describedpreviously.36,37. Defects in the ultrastructure of cilia have beenfound in patients with bronchiectasis, unrelated to immotile ciliasyndrome, but these may not be of clinical importance38–40.Mucus, once secreted, can become highly viscoelastic and adhesiveas a result of imbalance between the mucins and water available atthe airway lumen.

Mechanical obstruction

Obstruction of an airway causes localized disease. It isparticularly important to consider the possibility of an inhaledforeign body in children. Other causes of obstruction include aslow growing tumour, lymphadenopathy in association with amycobacterial infection and twisting of the airways after lobarresection.

P. King / Paediatric Respiratory Reviews 12 (2011) 104–110108

Retention of secretions with secondary obstruction may have avery important role in the ongoing pathology of bronchiectasis.Cole felt this was a key mechanism in the pathogenesis14.

Immune dysfunction

Nearly all the aetiologic factors described to cause bronchiec-tasis impair host defense (e.g. obstruction, primary ciliarydyskinesia). However, there are certain conditions which arespecifically classified as disorders of immune function and theywill be discussed in this section.

The immune deficiency most classically associated withbronchiectasis is hypogammaglobulinaemia. Hypogammaglobuli-naemia may predispose to infections with pyogenic bacteria suchas S. pneumoniae. The incidence of hypogammaglobulinaemia inbronchiectasis has been reported to be between 3% and 10%41,42.Deficiency of immunoglobulin G (IgG) subclasses has beenreported with a wide range between different studies of 2% to48%. IgG subclass deficiency is not as clearly associated withinfections and there has been controversy about whether it isclinically significant43.

Human immunodeficiency virus (HIV) is an important cause ofbronchiectasis and has been described to occur with advanceddisease. Other immune deficiencies associated with bronchiectasisinclude deficiency of the major histocompatibility complex class 1(MHC-I), transporter associated protein deficiency (TAP-1), inter-feron gamma receptor deficiency and deficiency of the respiratoryoxidative burst.

Cancer may be a cause of bronchiectasis. Children who havereceived chemotherapy for acute lymphoblastic leukemia have anincreased risk. Hypogammaglobulinaemia may occur in thecontext of chronic lymphatic leukemia.

Some disorders of immune function have been considered to becharacterized by an overactive response. Allergic bronchopulmon-ary aspergillosis is thought to arise from an intense allergicreaction to a common fungal commensal Aspergillus. In additionother pathogens may cause allergic bronchopulmonary disease.

The dominant causes of immune deficiency worldwide are thepresence of malnutrition/social disadvantage and extremes of age.Malnutrition/social disadvantage may have a key role in theimpairment of immune function and the development of bronch-iectasis in indigenous populations and developing nations. The onsetof a chronic productive cough is most common in young children andolder adult consistent with the relative impairment of immunefunction that occurs with extremes of age13. Childhood onsetbronchiectasis is often associated with rhinosinusitis (Figure 1C).

Rheumatic/inflammatory conditions

Rheumatoid arthritis (RA) has a strong association withbronchiectasis. The incidence of coexistent bronchiectasis in RAhas been described to be 1-3% and several studies report theprevalence on HRCT to be up to 30%. Bronchiectasis has beendescribed to occur both before and after the onset of RA. Recurrentrespiratory infections/bronchiectasis have also been described tobe prevalent in inflammatory bowel diseases. The reasons for thisassociation are not known.

Other conditions

There are a number of other conditions which are thought tohave an aetiologic role in bronchiectasis. Approximately 2% ofsubjects with alpha 1-antitypsin deficiency have bronchiectasis.Williams-Campbell syndrome is an inherited disorder of bronchialcartilage that presents with bronchiectasis in childhood. Aspira-tion may be important although this is controversial. In adults a

major cause to consider is smoking, up to 50% of subjects withchronic obstructive pulmonary disease have evidence of bronch-iectasis on HRCT.

MICROBIOLOGY

A large number of different pathogens have been described tobe present in the sputum of subjects with bronchiectasis. Thepattern of isolates does vary significantly between differentinstitutions/locations. The main two pathogens reported inprevious studies have been H. influenzae and P. aeruginosa. Otherprominent isolates include S. pneumoniae, Moxarella catarrhalis andnon tuberculous mycobacteria (NTM). Staphylococcus aureus isuncommon and its isolation suggests the possible presence ofcystic fibrosis. An important finding is despite the presence of goodquality purulent sputum samples 30-40% of specimens willdemonstrate no growth. Even when using bronchoscopy 30% ofspecimens will show no growth44.

The microbiology of bronchiectasis is also a dynamic processwith turnover of pathogens. Klingman et al assessed 28 patientswith bronchiectasis who had monthly sputum cultures for 2years45. Six patients had Brahmanella (or as it now is termed M.

catarrhalis) in their sputum chronically. Analysis of these isolatesdemonstrated a continuous turnover of strains with a new onebeing acquired on average every 2.3 months.

There is a change in the microbiologic flora in the airways aslung function declines. Subjects with normal lung functiongenerally have no bacteria isolated from their sputum. H. influenzae

is found is patients with moderately impaired lung function whilstP. aeruginosa is typically found in those with advanced disease46.

How the airways become colonized with bacteria is not known.This is a key event in the pathogenesis of this condition and shouldbe considered to be different from post-infectious bronchiectasiswhich has been described previously. The pathology studies ofWhitwell demonstrate that the bronchial walls are infiltrated withinflammatory cells. These cells may be responding to infectiousagents which have established a survival niche by invading into thebronchial wall.

Specific pathogens

Haemophilus influenzae is most common bacterium isolated inpatients with bronchiectasis. Roberts et al used selective culturemedia and techniques and reported that this bacterium waspresent in more than 70% of patients47. Sputum samples do notalways accurately reflect the microbiologic profile of the lowerairways. A bronchoscopy study that used protected bronchialbrush specimens and bronchial lavage found the presence of H.

influenzae in 55% of specimens. Nearly all the isolates are thenontypeable form.

After Haemophilus the next common pathogen in bronchiectasisis Pseudomonas aeruginosa. Pseudomonas is associated with worselung function, more sputum and hospitalizations, extensivedisease and worse quality of life. Pseudomonas species are ableto form biofilms. Biofilm forming bacteria are reported as having amucoid phenotype by microbiology laboratories and are virtuallyuntreatable.

The role of viral infections has not been well defined inbronchiectasis. Beecroft has described adenovirus as beingimportant in the development of bronchiectasis. As describedpreviously HIV has an important aetiologic role. There is nodefinitive data which demonstrates the role of viruses inexacerbations of bronchiectasis although they have recently beendescribed to be important in the context of COPD. Neutrophils frombronchiectasis subjects which are exposed in vitro to influenza Ahave decreased bacterial activity48.

P. King / Paediatric Respiratory Reviews 12 (2011) 104–110 109

OUTCOME

Cole’s vicious cycle proposes that bronchiectasis becomes aself-sustaining inflammatory airways disease that leads toprogressive lung damage. The pathology studies of Whitwelland the decline in lung function are consistent with this theory.Adults have also been described to develop progressively worsesymptoms over time as well decline in lung function. Factorsassociated with decline include volume of sputum23, systemicinflammation, colonization by P. aeruginosa and severe exacerba-tions25. Tsang and Tippoe describe in adults that there are 4 mainpatterns; 1), slowly progressive (the most common pattern) 2),rapidly progressive 3), indolent and 4) haemoptysis predominant.The outcome of bronchiectasis is therefore quite variable betweendifferent patients. Another feature is that there is often a long delaybetween the onset of symptoms and diagnosis. One study foundthat most patients had a chronic productive cough for more than20 years before a diagnosis of bronchiectasis was made28.

There may also be a variable pattern that occurs with differentages. Field followed up a large cohort of children with bronch-iectasis prospectively into adult life for more than 15 years49,50.She found that patients had the worst disease in early childhoodand generally tended to improve regardless of treatment whenthey became adolescents. We have assessed a large cohort ofpatients with childhood onset disease whose symptoms tended toeither improve or stabilize from about the age of 16 years thenbecame worse again over the age of 50 years13. This suggests thatthe optimal immune function of young adults may alter the courseof the clinical disease.

CHRONIC SUPPURATIVE LUNG DISEASE/CHRONIC BRONCHITIS

Many adults appear to have chronic infective bronchitis withsignificant sputum production and improvement with antibioticsbut do not have evidence of bronchiectasis on HRCT.

There are often significant logistical problems in obtainingHRCT scans in children. Chang et al have described the clinicalphenotype of children with a chronic wet cough as having chronicsuppurative lung disease (CSLD)51,52.

It has not been proven if CSLD in children and chronic infectivebronchitis in adults evolves into radiologic bronchiectasis but thisappears likely (at least in a proportion of patients) on the basis ofwhat is known about the pathogenesis of this condition. This doessuggest that it may be possible to change the natural history of thedisease by aggressive early intervention.

CONCLUSION

Bronchiectasis is a heterogeneous condition with a largenumber of potential contributory factors and poorly understoodpathogenesis. The vicious cycle hypothesis proposes that bronch-iectasis is characterized by a self-sustaining cycle of infection andinflammation that results in progressive lung disease.

Pathology studies have demonstrated infiltration of the walls ofthe small airways by a cellular infiltrate causing obstruction. Theinflammatory process damages the large airways causing bron-chial dilatation. Consistent with the pathological findings patientswith bronchiectasis tend to develop progressive decline in lungfunction and worse symptoms over time although in adolescencethis pattern may stabilize.

There are a large number of aetiologic factors that have beendescribed to cause bronchiectasis. It may be difficult to exactlyestablish their role in individual patients. It may be appropriate toconsider non-CF bronchiectasis as part of a spectrum of chronicinflammatory airways diseases that includes infective bronchitisand cystic fibrosis.

For a long time bronchiectasis had a low profile and remainedpoorly researched. Better understanding of the pathogenesis of thiscondition is likely to lead to improved outcomes and therapies forpatients.

Acknowledgements

The author would like to thank Associate Professor PeterHolmes for his help with this work.

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