Bronchiectasis in Systemic Diseases*

Mark Cohen and Steven A. Sahn

Chest 1999;116;1063-1074
DOI 10.1378/chest.116.4.1063
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© 1999 American College of Chest Physicians
Bronchiectasis in Systemic Diseases*
Mark Cohen, MD; and Steven A. Sahn, MD, FCCP
(CHEST 1999; 116:1063–1074)
Key words: bronchiectasis; inflammatory bowel disease; rheu-
matologic diseases
Abbreviations: AS 5 ankylosing spondylitis; CD 5 Crohn’s dis-
ease; HLA 5 human leukocyte antigen; HRCT 5 high-resolu-
tion CT; IBD 5 inflammatory bowel disease; LIP 5 lymphocytic
interstitial pneumonitis; NIP 5 nonspecific chronic interstitial
pneumonitis; RA 5 rheumatoid arthritis; RP 5 relapsing poly-
chondritis; SLE 5 systemic lupus erythematosus; TB 5 tuber-
culosis; UC 5 ulcerative colitis; YNS 5 yellow nail syndrome
B ronchiectasis is defined as an abnormal, irrevers-
ible dilatation of the bronchi. It is not a disease
per se, but it represents the end stage of a variety of
pathologic processes.1 Laennec first described the
clinical entity of bronchiectasis in 1819, but the
clinical pattern of bronchiectasis has changed in the
last century due to the early treatment of necrotizing
pneumonias, better control of tuberculosis (TB), and
the prevention of predisposing pulmonary infections
by routine immunization. Advances in medical treat-
ment have also lead to an increased survival to
adulthood of patients with cystic fibrosis, hypogam-
maglobulinemia, and immotile cilia syndrome, all of
which predispose to bronchiectasis.
Recently, bronchiectasis has been described as “an
orphan disease,” with a prevalence estimated to be
low and decreasing,2 but no reliable statistical esti-
mates are available. The true prevalence of bronchi-
ectasis most likely is underestimated, as less severe
forms of bronchiectasis have been documented with
the increased use of high-resolution CT (HRCT).3–11
It should also be recognized that an underlying cause
for bronchiectasis is found in , 40% of patients,12
and that HRCT features alone do not allow a
confident distinction between idiopathic bronchiec-
tasis and known causes of bronchiectasis.13,14
The most commonly cited classification of bron-
chiectasis was based on bronchographic and autopsy
findings and included three patterns of bronchiecta-
sis: cylindrical, varicose, and saccular or cystic.15
*From the Division of Pulmonary and Critical Care Medicine,
Allergy and Clinical Immunology, Medical University of South
Carolina, Charleston, SC.
Manuscript received March 1, 1999; revision accepted May 13,
1999.
Correspondence to: Steven A. Sahn, MD, FCCP, Division of
Pulmonary and Critical Care Medicine, Allergy and Clinical
Immunology, 96 Jonathan Lucas St, Suite 812, PO Box 250623,
Charleston, SC 29425; e-mail: sahnsa@musc.edu
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© 1999 American College of Chest Physicians
However, the clinical usefulness of designating bron-
chiectasis to one of these patterns is questionable,
and no study to date has shown a clinical, epidemi-
ologic, or pathophysiologic difference between these
patterns.16
This review will discuss the major systemic dis-
eases associated with bronchiectasis and will de-
scribe specific diagnostic and therapeutic modalities
apart from the traditional interventions for any type
of bronchiectatic process. We will exclude diseases
that are associated with abnormal host defenses
(hypogammaglobulinemias, ciliary dyskinesis); ge-
netic disorders (cystic fibrosis, a1-antitrypsin defi-
ciency); and postinfectious processes, including al-
lergic bronchopulmonary aspergillosis, since these
processes predominantly affect the lung (Table 1).
Rheumatologic Diseases
Rheumatoid Arthritis
Pleuropulmonary involvement is one of the extra-
articular manifestations of rheumatoid arthritis (RA),
with a prevalence estimated at , 5%.17,18 Pleuropul-
monary manifestations of RA include the following:
interstitial pulmonary fibrosis; pleural disease (pleu-
ritis with or without effusion, sterile or septic empy-
ema, necrobiotic nodules with bronchopulmonary
fistula, or pyopneumothorax); rheumatoid necrobi-
otic nodules; respiratory tract infection, especially
typical and atypical TB; bronchiolitis obliterans with
or without organizing pneumonia; pulmonary vascu-
lar lesions and pulmonary hypertension; apical fibro-
bullous disease; thoracic cage immobility; and upper
airway dysfunction due to cricoarytenoid arthritis.19
Bronchiectasis is typically not mentioned as an extra-
articular manifestation of RA; however, an associa-
tion between the two disorders is well recognized.
Bronchiectasis in patients with RA received con-
siderable interest earlier in this century. Their asso-
ciation was discounted on the argument that pulmo-
nary TB was more common in patients with
rheumatoid disease and that the bronchiectasis was
related to TB.20 The latter has been disproven by
recent studies where no historical or radiographic
evidence of previous TB was found in patients with
RA and bronchiectasis.11,19,21,22
To further strengthen the association between RA
and bronchiectasis, Walker21 found the incidence of
bronchiectasis to be 3.1% in RA, compared to 0.3%
CHEST / 116 / 4 / OCTOBER, 1999 1063
 Table 1—Conditions Associated With Bronchiectasis
Predominantly affecting the lung
Postinfectious bronchial damage
Bacterial: Staphylococcus aureus, Haemophilus influenza,
Mycoplasma pneumoniae, anaerobes (recurrent aspiration),
Mycobacterium tuberculosis, and atypical mycobacteria
(Mycobacterium avium-complex)
Fungus: Aspergillus (including allergic bronchopulmonary
aspergillosis), histoplasmosis and coccidioidomycosis
Viral: measles, pertussis, and adenovirus
Abnormal host defense
Immune deficiency:
Primary: selective or panhypogammaglobulinemia,
complement deficiency
Secondary: malignancy, chemotherapy, posttransplant, etc
Ciliary dyskinesia: immotile cilia, Kartagener’s syndrome,
Young’s syndrome, secondary ciliary dyskinesia
Congenital
Cystic fibrosis and variants
a-1 protease inhibitor deficiency
Unilateral hyperlucent lung (Swyer-James syndrome)
Tracheobronchomegaly (Mounier-Kuhn syndrome)
Congenital cartilage deficiency (Williams-Campbell syndrome)
Pulmonary sequestration
Mechanical bronchial obstruction
Intrinsic: foreign body, tumor, viscid secretions
Extrinsic: right middle lobe syndrome, adenopathy
Postinflammatory pneumonitis
Aspiration
Inhalation of toxic gases
Diffuse panbronchiolitis
Idiopathic pulmonary fibrosis
Systemic diseases
Collagen vascular diseases:
RA
Sjögren’s syndrome
AS
RP
SLE
Marfan’s syndrome
Inflammatory bowel disease
UC
CD
Celiac disease
Sarcoidosis
YNS
AIDS
Endometriosis
Amyloidosis
in patients with osteoarthritis. He also noted that the
incidence among newly referred patients with RA
was 3.2%, demonstrating that the association was not
spuriously related to a more careful follow-up of
patients with these two diseases. When the incidence
of bronchiectasis was compared to pulmonary fibro-
sis in patients with RA, Walker found an incidence of
pulmonary fibrosis to be 1.6% in the same popula-
tion. In the series by Solanki and Neville,22 the
association of bronchiectasis and RA was 5.2%,
compared with 4.7% for pulmonary fibrosis and RA.
Therefore, the association of bronchiectasis and RA,
although rare, as is pulmonary fibrosis and RA,
should be considered as a real, rather than spurious,
association and should be included as a manifestation
of RA.
The association of bronchiectasis and RA has been
reassessed, with the identification of bronchiectasis
in 20 to 35% of patients with RA who have under-
gone HRCT.5– 8,11 These findings suggest a higher
frequency of bronchial abnormalities in RA than has
previously been reported in postmortem studies, in
which the prevalence of bronchiectasis ranged from
0 to 10%.2,23 Although bronchiectasis was detected
with a higher frequency in patients with respiratory
symptoms, HRCT findings of bronchiectasis were
identified in 8% of asymptomatic patients.6 To ex-
clude the effects of smoking, several studies have
shown that bronchiectasis has been identified in RA
patients who were never smokers.6 – 8 The incidence
of concomitant interstitial pulmonary fibrosis was
low in most studies (# 10%),6 – 8,11 suggesting that
“traction bronchiectasis” is not responsible for the
presence of bronchiectasis.
The temporal relationship between bronchiectasis
and RA is still debated, but several explanations have
been proposed to account for this association. As
with most pleuropulmonary manifestations of RA,
bronchiectasis can precede or develop after the
onset of RA.15,24,25 In the former group, prior evi-
dence of bronchial infection and/or chronic bron-
chial suppuration has led to the hypothesis that
chronic bacterial infection plays a causative role in
triggering an immune reaction leading to articular
involvement.21–23,25 This hypothesis is supported by
the finding that RA starts at a younger age in patients
with bronchiectasis.26 The interval between bronchi-
ectasis and the onset of RA symptoms ranged from 1
to 34 years (mean, 19 years) in the series of Solanki
and Neville,22 and a mean of 36.5 years in men and
28.5 years in women in Walker’s series.21 However,
there is no evidence that patients with preexisting
bronchiectasis have more severe RA than those
without bronchiectasis,11,25 suggesting that it is un-
likely that chronic suppuration per se drives the
rheumatoid disease. If lung infection is causally
related to the onset of RA, it probably occurs by
allowing exposure to a range of bacterial antigenic
stimuli that triggers the disease in genetically predis-
posed individuals.25
In contrast, it has been suggested that several
factors related to RA itself or to its treatment may
increase the incidence of respiratory infections and
account for the delayed presentation of bronchiecta-
sis in patients with established RA. Despite in vitro
studies showing decreased neutrophil chemotaxis27
or defects in monocyte bactericidal activity28 in RA

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© 1999 American College of Chest Physicians
patients, two recent studies29,30 have shown no in-
creased incidence of infections when RA patients are
compared to control patients with osteoarthritis or
other soft tissue rheumatic diseases. Because of the
possible influence of antirheumatic drugs on the
lung, it has been reported that corticosteroids alone
may contribute to the development of bronchiectasis
by increasing the risk for infection and/or inhibiting
healing of the bronchial wall following infection.19,30
Of the disease-modifying drugs, only methotrexate
has been shown to be associated with an increased
incidence of opportunistic infections involving the
lung; however, most of these patients were also
receiving corticosteroids. Thus, an additive immuno-
suppressive effect may have been contributory.19,30,31
Early studies had suggested that secondary
Sjögren’s syndrome seen in RA could predispose
patients to recurrent respiratory infections and bron-
chiectasis.25,32,33 In disagreement to these studies,
two recent reports11,34 failed to observe any relation-
ship between the frequency of secondary Sjögren’s’
syndrome and the presence of bronchiectasis.
Another possibility is that RA and bronchiectasis
may share a common genetic predisposition. Hill-
arby and colleagues35 showed an association of hu-
man leukocyte antigen (HLA)-DR4 in patients with
RA and bronchiectasis and a slight increase in HLA-
DR1, which was not statistically different when
compared to either bronchiectasis alone or control
subjects. In this same study, subjects with RA and
bronchiectasis also showed an association with
DQA1*0501 (p 5 0.039), DQB1*0201 (p 5 0.0017)
and DQB1*0601 (p 5 0.0001), which were statisti-
cally increased when compared to RA alone.
DQB1*0601 was not statistically increased in fre-
quency in subjects with bronchiectasis alone when
compared to control subjects. Despite these find-
ings, there is no evidence that the association of
pulmonary complications with particular DQB vari-
ants represents a direct effect of genes at the DQB
locus on susceptibility to these respiratory features.
It appears likely that the final expression of rheuma-
toid disease represents an interaction between alleles
at several loci within the major histocompatiblility
gene complex.35
As stated previously, there is no evidence that
patients with preexisting bronchiectasis have more
severe RA than those without bronchiectasis11,23,25;
however, there is a decreased survival in patients
with the coexistence of these two conditions. Swin-
son and colleagues36 demonstrated that patients with
RA and bronchiectasis are 7.3 times more likely to
die during a 5-year follow-up period than the general
population, 5.0 times more likely to die than those
with RA alone, and 2.4 times more likely to die than
those with bronchiectasis alone. These differences
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© 1999 American College of Chest Physicians
were not attributed to age, sex, or RA disease
duration or severity. These data emphasize the im-
portance of bronchiectasis in the prognosis and
management of RA patients.
Sjögren’s Syndrome
Sjögren’s syndrome is a chronic, inflammatory,
autoimmune disorder characterized by the triad of
keratoconjunctivitis sicca, xerostomia, and, in over
half of cases, a connective tissue disorder. The
natural history and frequency of respiratory involve-
ment in primary Sjögren’s syndrome remain a sub-
ject of considerable controversy due to the differ-
ences in studied populations (primary, secondary, or
mixed Sjögren’s patients) and the methods used to
study the respiratory system, which vary from pre-
dominantly clinical to mainly functional. It is not
surprising, therefore, that the prevalence of pulmo-
nary abnormalities in Sjögren’s syndrome range from
9 to 75%.37– 41 Thus, it is problematic to assess the
incidence of bronchiectasis in primary Sjögren’s
syndrome.
Several pulmonary complications have been re-
ported in patients with primary Sjögren’s syndrome,
including lymphocytic interstitial pneumonitis (LIP),
pseudolymphoma and lymphoma,42,43 atelectasis,
bronchiectasis,39,44 and pulmonary hypertension.45
Other manifestations have been described in
Sjögren’s syndrome, but it has been difficult to
determine which of the manifestations is the result of
Sjögren’s syndrome and not of the underlying asso-
ciated connective tissue disease.46
It is believed that the invasion of mucous glands
in the tracheobronchial tree by lymphocytes re-
sults in atrophy and hyposecretion of these glands.
This leads to plugging of the respiratory tract by
inspissated secretions followed by atelectasis, in-
fection, and bronchial wall destruction, with the
consequent development of bronchiectasis.37,47 How-
ever, a lack of documentation of bronchiectasis in
recent studies of patients with primary Sjögren’s syn-
drome39 – 41,44,48,49 questions this association. In de-
fense of the hypothesis, most of these studies did not
include HRCT in the evaluation of their patients
and, therefore, lack the sensitivity to make the diag-
nosis of bronchiectasis.
In conclusion, pulmonary manifestations in pri-
mary Sjögren’s syndrome are common, but the pre-
cise pathophysiology and incidence is unknown.
Bronchiectasis may complicate the course of disease
in these patients and should be sought for in the
appropriate clinical setting with chest radiographs
and HRCT scans.
CHEST / 116 / 4 / OCTOBER, 1999 1065
Ankylosing Spondylitis
Pleuropulmonary involvement in ankylosing spon-
dylitis (AS) is an uncommon, yet well-recognized,
extra-articular manifestation of this disease. Rose-
now and associates,50 in a retrospective study of
2,080 patients with AS, reported the incidence of
pleuropulmonary involvement to be 1.2%. In smaller
and less detailed studies, the incidence varied from 0
to 30%. These studies were based almost entirely on
standard chest radiographs, with occasional patho-
logic confirmation.51–53
The most common thoracic finding is ankylosis of
the costovertebral junctions, severely limiting expan-
sion of the chest. In the report by Rosenow and
associates,50 apical fibrobullous disease and superin-
fection of these cavities with fungal (usually Aspergil-
lus) and mycobacterial (usually nontuberculous) or-
ganisms were the most common findings. Isolated
cases of pleural disease (pleural effusion, pleural
fibrosis, pneumothorax)50; localized pulmonary amy-
loidosis54; and cor pulmonale and bronchiolitis oblit-
erans with organizing pneumonia55 have been re-
ported. With the advent of HRCT, nonapical
interstitial lung disease, bronchiectasis, and medias-
tinal lymphadenopathy have been detected.10 Cas-
serly and colleagues10 found airway disease mani-
fested as bronchial wall thickening or bronchiectasis
in 6 of 26 patients (23%). Two of the six patients had
traction bronchiectasis in association with severe
apical fibrosis. Primary bronchiectasis was seen in
four patients, three of whom were current smokers;
in one patient, bronchiectasis was identified on plain
radiography.10
Relapsing Polychondritis
Relapsing polychondritis (RP) is a rare inflamma-
tory disease of unknown cause, primarily affecting
cartilage-containing tissues, with subsequent degen-
eration and fibrosis. Respiratory involvement has
been noted in 56% of patients and, in general,
indicates a poor prognosis, accounting for approxi-
mately 50% of deaths in those cases of RP where the
cause of death was determined.56
Respiratory tract involvement may occur early in
the course of RP, involving primarily the glottic,
laryngeal, and subglottic soft tissues with inflamma-
tion and edema, and frequently requiring tracheos-
tomy.56 –58 Later, there may be cartilaginous dissolu-
tion of any or all of the tracheal and bronchial
cartilages, leading to a peculiar type of obstructive
pulmonary disease. This is due to increased collaps-
ibility of the airways and/or fixed narrowing from
granulation tissue and fibrosis.57,58 The tracheobron-
chial tree narrowing is usually continuous through-
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© 1999 American College of Chest Physicians
out its length; however, the extent to which more
peripheral bronchi are involved is uncertain.57
Bronchiectasis involving large and medium-size
bronchi was described at autopsy59 and in a case
report utilizing HRCT.3 Whether or not bronchiec-
tasis is directly attributable to chondritis is unclear.
Bronchiectasis has been shown in regions of recur-
rent pneumonias, as well as in pneumonia-free re-
gions. It is thought that proximal obstruction of the
trachea and main bronchi may impair drainage of
secretions, predisposing patients to recurrent infec-
tion. Therefore, bronchial walls that have already
been injured by chondritis may be additionally weak-
ened.3
With the frequency and potential for sudden
decompensation of patients with RP, the importance
of surveillance and appropriate treatment of respira-
tory tract infections and consequent bronchiectasis
cannot be overemphasized.
Systemic Lupus Erythematosus
Thoracic involvement in systemic lupus erythem-
atosus (SLE) can be categorized as primary or
secondary. Primary involvement includes pleuritis
with or without effusion, alveolitis, interstitial fibro-
sis, lupus pneumonitis, bronchiolitis obliterans with
organizing pneumonia, obliterative bronchiolitis,
pulmonary vasculitis and hemorrhage, pulmonary
arterial hypertension, and pulmonary thromboem-
bolic disease. Secondary effects include basal atelec-
tasis from diaphragmatic dysfunction, opportunistic
infections, drug toxicity, and the pleuropulmonary
consequences of cardiac and renal failure.60 The
many reviews and case reports of pleuropulmonary
involvement in SLE reflect a great diversity in
prevalence and nature of abnormalities, with a
quoted incidence ranging from 7 to 100%, and a
clinical spectrum varying from acute fulminant lung
injury to indolent and chronic forms of interstitial
pulmonary disease.
Airways disease defined as bronchiectasis or bron-
chial wall thickening had not been reported until
Fenlon and coworkers9 described the HRCT find-
ings in patients with SLE. In this series, airways
disease was observed in 34% (12/34) of the cases,
with bronchiectasis reported in 21%. Chest radio-
graphs and pulmonary function tests were poor
predictors for airway involvement. There was no
regional predilection, with abnormalities equally dis-
tributed in the upper, mid, and lower zones. Nine of
the 12 patients (75%) with airways disease were
never smokers, suggesting that neither smoking nor
an increased susceptibility to its effects are the main
cause of its development. Of the 34 patients, 28
Reviews
patients (82%) denied respiratory symptoms, and
only 5 patients (15%) had abnormal findings on chest
examination.
The incidence of bronchial abnormalities in the
series of Fenlon and coworkers9 was similar to that
reported in the RA population, but was significantly
higher than suggested by reports in SLE patients
using chest radiographs and pulmonary function
testing alone.61
The cause of the bronchial abnormalities is un-
known, but it may be due to an increased suscepti-
bility to infection as seen in the RA population. More
studies are needed to evaluate the clinical incidence
and significance of bronchiectasis detected in asymp-
tomatic SLE patients. It is recommended that
HRCT be offered to patients with SLE whose
clinical, pulmonary function, and chest radiography
findings are equivocal or suggest the development of
early or possibly reversible airways disease.
Marfan’s Syndrome
Marfan’s syndrome is a connective tissue disorder
that is inherited as an autosomal dominant pattern
with variable expression. In its classical form, it
comprises abnormalities in the musculoskeletal, car-
diovascular, and ocular systems. Pulmonary manifes-
tations are estimated to occur in 10% of patients,62,63
the most common being spontaneous pneumotho-
rax62,64 and emphysema.65 Other presentations in-
clude interstitial parenchymal disease with honey-
combing,66 congenital malformations of the
bronchus, cystic pulmonary disease,63,67 and in-
creased susceptibility to respiratory infections due to
bronchiectasis.63,68 –70
The etiology of pulmonary manifestations is un-
known, but it logically could be explained by the
underlying connective tissue disorder. Currently, the
pathogenesis is believed to be related to abnormal
collagen cross-linking due to a biochemical defect in
the b-2 chain of type I collagen.71,72 The resultant
precocious weakness of the abnormal collagen in
tissues undergoing mechanical stress is termed abi-
otrophy.73 This weakness in pulmonary connective
tissue is unrelated to inflammatory disease of the
lung and could be expected to be progressive.74 The
progressive connective tissue weakness could explain
the various pulmonary manifestations previously
cited.
Inflammatory Bowel Disease
Ulcerative Colitis
Extraintestinal manifestations of ulcerative colitis
(UC) are common, occurring in up to 45% of
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© 1999 American College of Chest Physicians
patients, and include uveitis, arthritis, skin lesions,
and liver disease.75 In contrast, pulmonary involve-
ment in UC was thought to be rare, having been
reported in only 3 of 1,400 patients (0.21%) with
inflammatory bowel disease (IBD).76 It was not until
the publication by Kraft and coworkers77 that respi-
ratory involvement was included in the list of estab-
lished complications of IBD.78
Since then, five major clinicopathologic categories
of respiratory involvement have been described79,80:
(1) airway disease, including subglottic stenosis,
chronic bronchitis, chronic bronchial suppuration,
bronchiectasis, and chronic bronchiolitis; (2) inter-
stitial lung disease, including bronchiolitis obliterans
with organizing pneumonia, unspecified interstitial
lung disease, and pulmonary infiltrates and eosino-
philia; (3) necrobiotic parenchymal nodules; (4) se-
rositis with pleural or pericardial effusions; and (5)
pulmonary vascular disease, including vasculitis and
pulmonary embolism. The majority of patients re-
ported in the literature disease (43 to 63%) have had
airway disease,79 – 83 with chronic bronchitis and
bronchiectasis being the most common, 21% and
25%, respectively.80
The typical patient with airway involvement has no
history of childhood respiratory illnesses, is a non-
smoker, and unexpectedly develops chronic cough
productive of variable amounts of sputum. Camus
and colleagues80 reported that respiratory symptoms
were diagnosed after IBD in 85% of cases. In 79% of
these cases (37/47), IBD was inactive, either because
of prior medical treatment or coloproctectomy. Re-
spiratory involvement predated IBD in 14%,
whereas IBD and respiratory involvement were con-
comitant in 5%.
The pathogenesis of UC causing bronchiectasis is
unknown, but both morphologic and developmental
similarities exist between colonic and bronchial epi-
thelium. Both are derived from primitive gut and
have columnar epithelia with goblet cells and sub-
mucosal mucous glands. The nonspecific inflamma-
tory changes beneath the bronchial epithelium are
histologically similar to those seen beneath colonic
epithelium in UC.84,85 It was initially thought that a
systemic immunologically mediated phenomenon
(ie, circulating immune complexes) was responsible
for the bronchial and colonic changes and would
tend to remit after colectomy. However, the rapid
appearance and progression of chronic bronchial
suppuration after colectomy suggested that circulat-
ing inflammatory mediators or reactive oxygen radi-
cals known to be released by the inflamed colonic
mucosa are not the primary cause for bronchopul-
monary inflammation.80,86 An autoimmune process is
supported by Butland and associates,82 in which a
majority of their patients had a positive family history
CHEST / 116 / 4 / OCTOBER, 1999 1067
of autoimmune phenomenon and positive antinu-
clear antibody and anti-smooth muscle antibodies.
An alternative hypothesis has suggested that com-
mon irritants (antigens) that are inhaled and ingested
sensitize the lung and gut-associated lymphoid tis-
sue, and future mucosal breaks could lead to an
allergic inflammatory response in both sites.81,87
While the immunopathogenesis of bronchopulmo-
nary-associated complications in UC remains un-
known, therapy has been guided by case reports and
not by controlled studies. In contrast to the treat-
ment recommendations for some of the other ex-
traintestinal manifestations of IBD, colonic surgery
should not be proposed in an attempt to control the
airway disease.80 Instead, a long-lasting and striking
response has been seen following inhaled or systemic
corticosteroids, an uncommon finding in chronic
bronchitis or bronchiectasis.80 – 83,88 Inhaled cortico-
steroids were more effective in treating chronic
bronchitis than in treating bronchiectasis.80 How-
ever, the apparent ineffectiveness of inhaled cortico-
steroids may not relate to the failure of these drugs,
but rather to their impaired disposition in airways
filled with inspissated secretions. In two of these
cases, Camus and coworkers80 performed multiple
BALs with methylprednisolone with a dramatic re-
sponse. In summary, inhaled corticosteroids should
be used early as a first-line treatment in patients with
IBD and bronchial involvement. For nonresponders,
topical corticosteroids via BAL or systemic cortico-
steroids should be attempted prior to colonic surgical
intervention.
Crohn’s Disease
The involvement of respiratory manifestations in
patients with Crohn’s disease (CD) is even more
unusual than in those with UC.80 A review of the
literature only finds a few cases of pulmonary paren-
chymal involvement in CD patients, including the
following cases: eight cases of interstitial lung dis-
ease,89 –91 one case of bronchiolitis obliterans orga-
nizing pneumonia,80 one case of lung infiltrates with
peripheral eosinophilia,80 and three cases of chronic
bronchitis.77,80 No cases of bronchiectasis have been
reported in any of the large IBD studies,75,76,80 but in
none of these studies has HRCT scan been used to
evaluate the presence of bronchiectasis. A case re-
port of bronchiectasis following colectomy for CD
was recently reported.92 This patient presented with
a purulent productive cough 3 months postcolec-
tomy and bronchiectasis on HRCT that was absent
on a HRCT 2 months after colectomy. Although the
association of bronchiectasis and CD in this case
raises the possibility of a chance association, strong
circumstantial support for a real association includes
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© 1999 American College of Chest Physicians
a clear temporal relationship to colectomy and,
unlike idiopathic bronchiectasis, a repeated failure to
identify bacterial pathogens and an impressive re-
sponse to oral corticosteroids.92
Sarcoidosis
Sarcoidosis is a disease of unknown cause charac-
terized by an excess of helper T lymphocytes at sites
of involvement.93 In the lung, the noncaseating
granulomas occur mainly in the peribronchial,
perivascular, and subpleural areas, and in the bron-
chial mucosa. Endobronchial manifestations of sar-
coidosis are common, as confirmed by blind biopsies
of apparently normal bronchial mucosa that yield
granulomas in up to 37% of patients.94 Although
common, it is rarely of sufficient magnitude to cause
bronchial narrowing and atelectasis that result in
symptoms and disability.95,96
Endobronchial sarcoid may produce reversible
narrowing of the tracheobronchial tree by inflamma-
tory edema or an endobronchial mass, or it may
produce permanent narrowing due to cicatricial ste-
nosis.97–100 The majority of the reports suggest that
bronchial narrowing, either inflammatory or cicatri-
cial, occurs only in the late stages of the disease,
when there is extensive pulmonary fibrosis. How-
ever, there are reports of bronchial stenosis in
patients with normal chest radiographs99 or stage II
disease.96,101
Therefore, the pathogenesis of bronchiectasis in
sarcoidosis can be largely attributed to “traction
bronchiectasis” secondary to anatomic distortion
from pulmonary and peribronchial fibrosis. How-
ever, the development of localized bronchiectasis in
patients without extensive fibrosis can be explained
either by endobronchial granulomas with bronchial
mucosal scarring or a disease akin to the right-
middle-lobe syndrome.
Endobronchial sarcoidosis has received little at-
tention as a cause of bronchiectasis; however, bron-
chographic studies in 11 patients with bronchosteno-
sis revealed bronchiectasis in 5 patients.96 In four
patients, there was mild bronchial dilatation and loss
of the normal distal tapering, and one patient had
saccular bronchiectasis. The development of bron-
chiectasis in these cases may be due to destruction or
weakening of the bronchial wall by granulomatous
inflammation. In no other condition, except TB, has
the combination of widespread bronchostenosis and
bronchiectasis been described to occur together.
This combination should be highlighted as an impor-
tant consequence of bronchial lesions in sarcoidosis.
Although rare, the development of bronchiectasis
as a result from right-middle-lobe syndrome has
Reviews
been described.102,103 In these two cases, minimal
adenopathy or bronchostenosis was seen; however,
chronic lymphadenitis was evident, explaining the
interference with lymphatic drainage rather than
mechanical obstruction from adenopathy. A vicious
cycle of inadequate drainage, nonspecific inflamma-
tion, and secondary lymphadenopathy in the drain-
age pathway could account for the bronchial wall
destruction and development of bronchiectasis.
Yellow Nail Syndrome
Yellow nail syndrome (YNS) is a rare entity, and its
diagnosis is based on clinical criteria since there are
no pathognomonic laboratory tests. Samman and
White104 first described the association of yellow
nails with primary lymphedema in 1964 and termed
it the “yellow nail syndrome.” Two years later,
Emerson105 described the full triad of slow-growing
yellow nails, lymphedema, and pleural effusions; in
1972, Hiller and colleagues106 reported that the
presence of two of the three symptoms was sufficient
to establish the diagnosis. Recently, the frequent
association of rhinosinusitis107 and the more uncom-
mon association of bronchiectasis106,108 –114 with YNS
may warrant its recognition as part of the syndrome.
Over 100 cases of YNS have been reported since
its original description, with a male to female ratio of
1:1.6.113 The median age of onset is 40 years, but it
has been recognized as early as birth105,115,116 and as
late as the seventh decade.106,117
Impaired lymph drainage is thought to be the
underlying defect that is responsible for the varied
clinical findings in patients with YNS. This theory is
supported by lymphangiographic findings that in
most patients showed a paucity of hypoplastic or
dilated lymphatics.104,105,113,118,119 Electron micros-
copy has120 shown dilated but otherwise normal
lymphatics, suggesting n obstruction of lymph flow
either in the major lymph vessels or at the lymph
nodes. The mechanism underlying the lymphatic
malformation has not been defined, but a genetic
predisposition has been suggested.116 The wide
range in age and type of onset of YNS suggests that
a precipitating event (such as infection, hypostasis,
insect bite, or injury) increases local capillary perme-
ability, and increasing the load on the already defi-
cient lymphatic system may be required.104
Sixty-three percent of the published cases of YNS
had pleuropulmonary symptoms. Respiratory tract
involvement was the initial symptom in 29% of the
cases, and pleural effusions were found in 36% of all
cases.113 The majority of patients often had a 10- to
20-year history of recurrent attacks of chronic bron-
chitis occasionally associated with bronchographi-
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© 1999 American College of Chest Physicians
cally or HRCT-verified bronchiectasis,106,108 –114
chronic sinusitis, pneumonia, or pleuritis.
The pathogenesis of bronchiectasis in YNS is
unknown. It is recognized, however, that bronchi
and bronchioles are richly supplied with lymphatic
vessels, with one network in the mucosa and another
in submucosal tissue.121 Therefore, it is thought that
bronchiectasis in YNS may be related to hypoplasia
of the bronchial lymphatics, similar to that described
previously in the lower limb lymphangiographic
studies.106,110 Other possible mechanisms for the
development of bronchiectasis include immunologic
abnormalities that have occasionally been described
in association with this condition. These include
hypogammaglobulinemia,109,122 low circulating B
cells,123 and macroglobulinemia.124 All of these
mechanisms, alone or in combination, will increase
the susceptibility to recurrent infections and will
impair airway defenses, with the consequent de-
struction of airways and development of bronchiec-
tasis.
The clinical prognosis of YNS has been difficult to
assess due to varying degrees of severity. No deaths
secondary to YNS have been reported, and partial or
complete recovery of the nail symptoms have oc-
curred in 30% of patients, with occasional relaps-
es.113 The lymphedema, pleural effusions, and bron-
chiectasis appear to be persistent and should be
treated symptomatically.
AIDS
Pulmonary manifestations in patients with AIDS
have been extensively described and include a wide
range of infections, as well as inflammatory and
neoplastic processes.125–128 However, the occurrence
of bronchiectasis has rarely been noted.4,129 –132 The
incidence of bronchiectasis in the HIV-infected pop-
ulation remains to be established, since it is fre-
quently undiagnosed because of a low index of
suspicion and because chest radiographs may be
normal or nonspecific.
The etiology of bronchiectasis in AIDS patients is
likely to be multifactorial, but recurrent bronchopul-
monary infection is probably one of the most impor-
tant contributing factors.4,129 –132 Vulnerability to in-
fection within the tracheobronchial tree may indicate
direct effects of HIV infection on the pulmonary
system. In addition to T-cell dysfunction, impaired
function of pulmonary monocytes and macrophages
and an abnormal humoral immune system predis-
poses this population to infections with resultant
airway and parenchymal injury.133–135
Moskovic and associates,129 in an evaluation of 11
patients with AIDS and Pneumocystis carinii pneu-
CHEST / 116 / 4 / OCTOBER, 1999 1069
monia by HRCT, found evidence of bronchial wall
thickening in association with parenchymal consoli-
dation in 9 patients, findings specifically suggestive
of “reversible bronchiectasis.”136 Interestingly, in
these cases, the degree of bronchial wall thickening
did not appear related to the degree of consolidation.
In two additional cases, there was evidence of bron-
chial dilatation, distinct from cystic or destructive
parenchymal lesions. Therefore, these authors sug-
gest that inflammation caused by P carinii pneumo-
nia affects not only distal airspaces but larger proxi-
mal airways as well.129
McGuinness and coworkers4 further documented
the occurrence of bronchiectasis on CT scans in 10
HIV and/or AIDS patients in the absence of myco-
bacterial infection or a history of prior recurrent
pyogenic infections. In these series, 6 of the 10
patients with a history of recent pneumonia demon-
strated bronchiectasis on CT within 4 weeks of their
only known episode of pneumonia, while 3 of the
remaining 4 patients demonstrated bronchiectasis
within 16 weeks of their first documented episode of
pneumonia. In eight cases, bronchiectasis was noted
to be multilobar despite radiographic evidence of
infection limited to only one or a few lobes.
The extent of bronchiectasis in the series of
McGuinness and coworkers4 appears to exceed that
which might have been anticipated given the brief
time interval between the onset of infection and the
development of bronchiectasis. This shortened time
frame suggests that AIDS patients have an acceler-
ated form of bronchiectasis4 or that previous pulmo-
nary infections were undocumented as a result of
their immunocompromised status.
The possibility of nonspecific chronic interstitial
pneumonitis (NIP) or LIP as an etiologic factor for
bronchiectasis in this population has been suggested.
Two patients have been reported to have CT-proven
bronchiectasis without antecedent histories of infec-
tion and transbronchial biopsy evidence of NIP and
LIP.4 In larger studies of AIDS patients with NIP or
LIP, bronchiectasis has not been mentioned, but
none of these studies used CT to evaluate for
bronchiectasis.137–141
Despite the small number of reports on bronchi-
ectasis in HIV/AIDS patients, it seems appropriate
to consider its inclusion as one of the pulmonary
manifestations of HIV infection. Before this is ac-
cepted, a large prospective study, including HRCT
studies, needs to be undertaken clarify the incidence
of bronchiectasis, as well as to evaluate its distribu-
tion across the various HIV risk groups, its natural
history, and the interplay of the multiple factors that
may be involved in its pathogenesis.
As the life expectancy of HIV-infected patients
increases with the new antiretroviral and protease
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© 1999 American College of Chest Physicians
inhibitor agents and the improved prevention and
treatment of opportunistic infections, the incidence
and comorbidity of bronchiectasis in these individu-
als could become important.
Miscellaneous
Bronchial endometriosis with bronchiectasis in a
60-year-old woman with cyclic hemoptysis for 30
years has been reported.142 The relationship be-
tween pulmonary endometriosis and bronchiectasis
remains uncertain. Recurrent bleeding in the airways
and interstitium with subsequent inflammation and
healing process may be a possible mechanism for the
development of bronchiectasis. Infection in the area
of bleeding is another possibility.142
Nodular pulmonary amyloidosis was thought to be
the cause of bronchiectasis presumably secondary to
compression of a bronchus.143 Secondary amyloid-
osis has been associated with bronchiectasis in five
reported cases. In four of these, amyloid deposition
was associated with a previous history of TB followed
by fibrosis and traction bronchiectasis.144 The re-
maining case was that of a 42-year-old man with
long-standing recurrent infections and the develop-
ment of bronchiectasis and amyloid deposition.145
Bronchiectasis in association with celiac disease
was reported in a 48-year-old woman with chronic
fatigue and purulent productive cough and wheez-
ing.146 The temporal relationship of her bronchiec-
tasis and celiac disease, and the subsequent stabili-
zation of her symptoms and improvement in
pulmonary physiology following treatment with in-
haled corticosteroids suggests a relationship between
the two conditions. The cause of the association of
pulmonary disorders with celiac disease remains
poorly defined. Absorption of an extrinsic allergen or
immune complexes through an abnormal GI mucosa
may lead to the pulmonary disease.147 Alternatively,
the association of celiac disease with HLA status and
various autoimmune diseases148 suggests that a com-
mon disturbance in immunity may underlie both
celiac disease and pulmonary disorders.
Conclusion
Bronchiectasis is considered an uncommon disor-
der; however, with the advances in modern medi-
cine, the recognition of this disorder is increasing
due to the use of HRCT and to the prolonged life
span of multiple diseases that have allowed the time
for the development of bronchiectasis. This review
intends to present the systemic diseases that have
been associated with bronchiectasis and, therefore,
Reviews
to stimulate the physician to search for the develop-
ment of bronchiectasis in these disorders, since
morbidity and mortality in these patients should
decrease if appropriate treatment is begun early. In
compiling all of the available information in the
English literature related to bronchiectasis in sys-
temic diseases, it is evident that there are a lack of
studies for a condition that is probably underdiag-
nosed and undertreated.
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Reviews
 Bronchiectasis in Systemic Diseases*
Mark Cohen and Steven A. Sahn
Chest 1999;116; 1063-1074
DOI 10.1378/chest.116.4.1063
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