Bronchiectasis

1. ETIOPATHOGENESIS OF
BRONCHIECTASIS
By Dr.Amal Thankachan

2. What is bronchiectasis ?
• Bronchiectasis is derived from the Greek
words:
Bronckos – airway
Ectasis – widening
• It is a chronic lung condition defined as the
abnormal irreversible dilatation of the
bronchi,where the elastic and muscular tissue
is destroyed by acute or chronic inflammation
and infection.

3. • Bronchiectasis represents the end stage of a
variety of pathologic processes that cause
destruction of the bronchial wall and its
surrounding supporting tissues.
• Etiologies include prior lung infection, systemic
inflammatory disorders, and genetic disorders of
host defense’
• However, bronchiectasis is considered to be
idiopathic in up to half of the affected individuals.

4. Pathophysiology
• As bronchiectasis is an acquired disorder, its
pathophysiology is commonly described as
distinct phases of infection and chronic
inflammation.
• The interaction between these phases
establishes a vicious circle in which the end
result is the destruction of the bronchi and the
accompanying clinical symptoms.

5. • Various mechanisms operate to produce
permanent, pathologic dilation and damage of
the airways.
• They may be in of in terms of traction,
pulsion, and weakened tensile strength of
the airways.
• In most cases the pathogenesis becomes
invariably linked with and propelled by the
destructive effects of chronic infection.

6. • As the lung undergoes fibrotic changes
consequent to disorders such as sarcoidosis,
interstitial lung disorders or infections such as
tuberculosis, local retractile forces result in
fixed dilation of the airways, or “traction”
bronchiectasis.
• The prototypic “pulsion” bronchiectasis
permanent airway dilatation as a result of
intense inflammation originating in the lumen

7. • The first stage in the development of
bronchiectasis -is an initial infective insult to the
airways, which triggers a mucociliary response.
• Micro-organisms trigger the release of toxins and
an inflammatory response within the airways.
• This inflammatory response includes the release
of neutrophils, lymphocytes and macrophages
within the bronchial lumen.

8. • Neutrophils also alter the function of the cilial
epithelium, leading to changes in cilial beat
frequency and mucous gland hypersecretion.
Both processes compromise mucociliary
clearance.
• Weakness of the airways-eg postinfectious
bronchiectasis

9. Pathophysiology

10. MICROBILOGY
“vicious circle” phase of bronchiectasis is dominated
by the influx of neutrophils. Neutrophils enter the airway lumina through gaps
between epithelial cells ,Neutrophils are attracted by the release of
chemokines such as in IL-8 and leukotriene B4 (LTB4) from macrophages, and
IL-17 from Th17 cells ,

11. • When Initial defenses are unable to contain
the infection Robust immune response
by airway epithelial cells and phagocytes by
Release of inflammatory cytokines and
chemokines that include macrophage
inflammatory protein-2, IL-8, and TNF-α.

12. • Airway infiltration by predominantly neutrophils,
macrophages and lymphocytes causes damage to
the airway epithelium
Through the release of various proteolytic
enzymes such as neutrophil elastase and
metalloproteinases
• Erosion of mucosal barriers, creating
microabscesses that can harbor bacteria

13. Neutrophil
elastase
Ciliary
dysfunction
Increased
mucus
secretion
Mucous
gland
hyperplasia
Impair
opsonization
of bacteria

14. Predisposing or Associated Conditions
• POSTINFECTIOUS CONDITIONS
• Childhood lower respiratory tract infections
• Granulomatous infections
• Necrotizing pneumonias in adults
Other respiratory infections

15. HERITABLE STRUCTURAL
ABNORMALITIES
• Primary ciliary dyskinesia
• Williams-Campbell syndrome
• Mounier-Kuhn syndrome
• Marfan syndrome

16. IDIOPATHIC INFLAMMATORY
DISORDERS
• Sarcoidosis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Systemic lupus erythematosus
• Sjögren syndrome
• Inflammatory bowel disease
• Relapsing polychondritis

17. INHALATION AND OBSTRUCTION
• Gastroesophageal reflux/aspiration
• Pneumonia
• Toxic inhalation/thermal injury
• Postobstruction accident
• Foreign body
• Allergic bronchopulmonary aspergillosis/mycosis
• Tumors, benign and malignant
• Extrinsic airway compression

18. MISCELLANEOUS
• HIV infection/AIDS
• Yellow nail syndrome
• Radiation injury
• Lung fibrosis

19. CYSTIC FIBROSIS(mucoviscidosis)
• CF is caused by a mutation in chromosome 7
q -CFTR gene.
• It is the most common autosomal recessive
disorder among whites
• The CFTR protein produced by this gene
regulates the movement of chloride and
sodium ions across epithelial cell membranes

20. • Cl ion help to lyse mucus
• Pt wil hv recurrent pneumonia
• Mcc-staphylococcus aureus
• Psueudomonas aeroginosa – with the help of
biofilm formation
• Burkholderia cepacia –pneumonia mc associated
with increased mortality
• CF and CF variants are one of the most common
causes of bronchiectasis

22. Youngs syndrome
It is seen only in males ,the genetic basis for
Young syndrome is not know- Possible
mechanism is ciliary dysfunction
clinical features of Youngs syndrome
• Bronchiectasis and recurrent LRTI
• sinusitis
• Infertility-obstructive azoospermia

23. DISORDERS OF IMMUNITY
• Primary diseases that result in
immunodeficiency may devolve from
mutations that impair B or T lymphocytes and
cause abnormal humoral immunity,cellular
immunity, or both
• Common variable immunodeficiency, or
acquired hypogammaglobulinemia is the most
frequent syndrome recognized in this group of
diseases.

24. Acquired Hypogammaglobulinemia
• Although there are normal numbers of
circulating B lymphocytes, they fail to
differentiate into antibodyproducing cells.
• This results in particular vulnerability to
infections with encapsulated bacteria such
• S. pneumoniae,
• H. influenzae,
• S. aureus, and P. aeruginosa.

25. • Other disorders of immunity include
• Hyper-IgM or hyper-IgE(Job syndrome)
• Impaired production of cytokines secreted by
type 1 helper T cells such as interferon-γ (IFN-
γ) and TNF-α, cytokines
• They are known to be important in controlling
such infections.
• Increase the susceptibility of individuals to
pyogenic bacteria and NTM organisms

26. Thymic hypoplasia resulting in abnormal
cellular immunity (DiGeorge syndrome)
severe combined immunodeficiency
syndrome, “bare lymphocyte” syndrome,
Wiskott-Aldrich syndrome (an X-linked
recessive illness associated with small
platelets and eczema)
Ataxia-telangiectasia syndrome

27. CILIATED EPITHELIUM
ABNORMALITIES

28. • Each ciliated epithelial cell possesses
approximately 200 cilia. The direction of ciliary
beating is determined by the orientation of
the central pair of microtubules.
• Dysfunction of the ciliary apparatus may
involve a variety of structural abnormalities in
the cilia or disorganization of the ciliary axes.

29. • A variety of abnormalities have been
described
• Including the complete or partial absence of
outer or inner dynein arms
• A lack of radial spokes
• Disordered microtubule arrangements,ciliary
disorientation etc

30. • PCD (primary ciliary dyskinasia )with situs
inversus universalis is known as Kartagener
syndrome
• The patients have a marked tendency toward
colonization and infection with H. influenzae.

31. 1
• Ineffective beating of the ciliated cells
2
• Stagnation and accumulation of mucus
3
• early-onset refractory or recurrent infectionsof the upper and lower respiratory tract
Bronchiectasis is a common sequela of PCD and it typically involve the
dependent zones, including the lower lobes, right middle
lobe, and/or the lingular segment of the left upper lobe

32. Bronchiectasis: Kartagener syndrome.-
CXR-shows dextrocardia with basal predominant linear opacities -bronchial
wall thickening and bronchiectasis.
Axial chest CT shows dextrocardia and severe, cystic bronchiectasis

33. BRONCHIAL CARTILAGE OR ELASTIC
FIBER DEFECTS
• Mounier-Kuhn syndrome, or
congenitaltracheobronchomegaly
• It is a rare disorder associated with gross
enlargementor dilation of the trachea and segmental
bronchi
• The underlying defect is atrophy and even absence of
elastic fibers and smooth muscle tissues of the large
airways.
• In addition, primary or secondary atrophy of the
connective tissue between the rings may result in
outpouchings or diverticula, potentially serving as
reservoirs for recurrent infections

34. Congenital tracheobronchomegaly (Mounier-Kuhn syndrome) with
bronchiectasis. This 73-year-old woman has had recurring
respiratory infections throughout her adult life
• B-The dilated trachea with prominent cartilaginous rings is
confirmed on a CT scan (between arrows).
• C, Not only is the trachea Enlarged, but the main-stem bronchi
are dilated (between arrows).

35. CT images show multifocal, thin-walled cystic bronchiectasis associated
with dilated trachea and central bronchi

36. • Mounier-Kuhn patients may present in their
early years or as late as the fourth decade
with recurring lower respiratory infections
• In advanced stages, airway collapsibility may
result in severe airflow obstruction.

37. Williams-Campbell syndrome
• Williams-Campbell syndrome or congenital
bronchial cartilage deficiency syndrome-It is
another rare disorder that tends to present
early in life with recurring infection and
bronchiectasis.
• The absence of cartilage from the segmental
to the first few generations of the
subsegmental airways is the typical finding in
Williams-Campbell syndrome

38. Williams-Campbell syndrome
This 50-year-old man had a lifelong history of recurring
respiratory infections and productive cough.
The airways are massively dilated with collections of
respiratory secretion spooling in some of the cystic spaces.

39. CONNECTIVE TISSUE ABNORMALITIES
• Marfan syndrome- due to mutation/defect in the
genes that produce fibrillin 1 (FBN1) gene.
• Morphologic anomalies seen with Marfan
syndrome have been traced to increased localized
production of TGF-β, a cytokine that increases
susceptibility to mycobacteria.
• Marfan syndrome has been linked to middle lobe
hypoplasia because the right middle lobe is the
most commonly affected lobe in NTM-associated
bronchiectasis.

40. IDIOPATHIC INFLAMMATORY
DISORDERS
• Mcc- Sarcoidosis
• Mechanisms -diffuse parenchymal scarring resulting in
traction and airway distortion, endobronchial
granulomatous inflammation including stricture with
poststenotic infection, or compression secondary to
hypertrophic peribronchial lymphadenopathy.
• Bronchiectasis has been seen in 20% to 35% of RA
patients undergoing HRCT scanning
• Potential causal mechanisms include increased
propensity for infections,either intrinsic to RA or
secondary to steroid or cytotoxictherapy

41. Axial chest CT through the upper lobes in a patient with sarcoidosis
shows biapical bronchiectasis with architectural distortion.

42. Sjögren syndrome
Lymphocytic inflammation
impaired function of
mucous glands
decreased volumes and
increased viscosity of mucus
poor clearance
chronic infection.

43. Inflammatory bowel disease &
Bronchiectasis
common epithelial targets
of autoimmunity -inhaled or
ingested.
cryptogenic
infection that
incites both
airway and
intestinal
inflammation
ulcerative colitis-
develop after
therapeutic
colectomy

44. Relapsing polychondritis – It is identified essentially
as progressive inflammation, weakness, and
deformity of cartilaginous structures, including the
ears, nose, larynx, and tracheobronchial
tree.Respiratory involvement is a common.
And is a major cause of mortality.
Bronchiectasis in such patients may bedue to
primary bronchial damage and/or recurrent
infection.
Bronchial
cartilage
inflammation
Airway
collapse
Airflow
limitation

45. Relapsing polychondritis. A, Axial inspiratory chest CT shows thickening of
the anterior two thirds of the trachea (arrowheads).
B, Axial chest CT performed following a forced vital capacity maneuver
shows excessive trachea collapse

46. ASPIRATION
1. Direct spillage of secretions from the
oropharynx, containing a plethora of
microorganisms, including microaerophilic and
anaerobic bacteria
2.Materials refluxed from the esophagus and/or
stomach-contain food particles, hydrochloric
acid Biliary or pancreatic secretions, and
microbes indigenous to the gut, including
Helicobacter pylori.

47. When Laryngeal protective functions are imperfect,
“microaspiration”
MCC is GERD , others including
(1) Depressed sensorium
(2) Altered brain-stem function
(3) Altered laryngeal structure/ Function
(4) Esophageal disorders -dysmotility, obstruction by tumors
or strictures, muscular dystrophy, achalasia,
tracheoesophageal fistulas, or lower esophageal sphincter
incompetence .
(5) Gastric dysfunction (dysmotility or outlet obstruction).

48. • Also chronic coughing, which stresses and dilates the
diaphragmatic ring, might disrupt the lower
esophageal sphincter and subject the esophagus to
distending forces
• An additional factor that could contribute to
gastroesophageal reflux disease is the medications
employed for pulmonary disorders, including
anticholinergics, β2-agonists, theophylline, and
corticosteroids, all of which impair lower esophageal
sphincter function and broadspectrum antibiotics,
which alter gastroesophageal flora.

49. Toxic inhalation / Thermal injury
• Acute and chronic inflammation of the
tracheobronchial tree, bronchiolitis, bronchiolitis
obliterans, and diffuse alveolar damage may be a
consequence of exposure to toxic metal fumes-
Aluminum,cadmium,chromium, nickel
• Toxic gases like ammonia, chlorine,
phosgene, sulfur dioxide
• Bronchiectasis may ensue because of either infectious
complications of the exposure, denuding of the ciliated
epithelium, or progressive fibrosis.
• chronic airway damage and bronchiectasis may evolve
following thermal or smoke injury.

50. POSTOBSTRUCTIVE DISORDERS
Foreign bodies/Tumors
Airway obstruction
Poor drainage
Recurrent/chronic infection
Bronchiectasis.
The more common tumor types include bronchogenic carcinomas particularly
the squamous cell variety,carcinoid tumors

51. • Extrinsic airway compression due most often
to hypertrophic lymphadenitis from
granulomatous diseases such as sarcoidosis or
infections, including tuberculosis or
histoplasmosis, may severely narrow or even
occlude large airways
• Focal bronchiectasis is seen particularly
those with disease limited to only one region/
one segment/ one lobe or even one lung

52. Postobstructive bronchiectasis. A–C, Axial chest CT shows severe narrowing of the
left lower lobe bronchus (arrow), due to carcinoid tumor.
Multifocal bronchiectatic consolidation (arrowheads) is present throughout the
left lower lobe

53. ALLERGIC BRONCHOPULMONARY
ASPERGILLOSIS
• Allergic bronchopulmonary
aspergillosis
• inhaled Aspergillus -lodged in
the airways.
• proliferating fungi form large
mucoid
Mucoid plugs
• medium-sized
bronchi
inflammation and
distention • thin-walled
bronchiectasis of the
central airways
characteristic
of ABPA

54. • In ABPA there are intense, immunologically
• mediated reactions to inhaled Aspergillus that
has
• lodged in the airways. The onglomerates that
fill the central airways; a
• sequela of this airway inflammatory process
and mucoid
• impaction is bronchiectasis

55. • Also in long-standing, inadequately controlled
ABPA/M. In such cases, extensive fibrosis and
airway distortion may evolve because of
uncontrolled inflammation.
 In these cases the patients may acquire
secondary airway pathogens including
P. aeruginosa or other gram-negative bacilli as
well as NTM.
 In these “burned-out” cases, the patients may
notdemonstrate asthma, eosinophilia,or elevated
levels of I

56. Bronchiectasis: allergic bronchopulmonary aspergillosis. Above are
Axial chest CT shows central bronchiectasis typical of allergic
bronchopulmonary aspergillosis.

58. IDIOPATHIC BRONCHIECTASIS
• Idiopathic is estimated to account for 25% to 50%
of cases
• It often has a characteristic phenotype of bilateral
lower lobe bronchiectasis and chronic
rhinosinusitis
• Genotyping studies of class I and class IImajor
histocompatibility complex molecules indicated
that allelic polymorphism for HLA-B (HLA-B5 and
HLA-B52), HLA-C (HLA-Cw*03 and and HLA-
DR/DQ (HLA-DR1/DQ5) are associated with
idiopathic bronchiectasis.

59. MISCELLANEOUS
• AIDS bronchiectasis has been identifiedin a
significant proportion of those undergoing CT
scans, including children
• Probable pathogenesis involves severe,
chronic, and recurrent infections with a
variety of opportunistic pathogens
• Also oxidative damage associated with
infection

60. • Yellow nail syndrome is an uncommon disorder
marked by the triad of: yellow, thick, dystrophic
nails; chronic lymphedema of the face, hands,
and lower extremities and pleural effusions.
• Recurrent sinusitis and lower respiratory tract
infections are common
• Abnormal lymphatic structure, increased vascular
permeability, deficient immunoglobulin
production, and/or ciliary dysfunction.

61. • Radiation therapy- typically delivered for
carcinoma of the breast or mediastinal tumors
including lymphomas may result in profound
damage to the central airways.
• Focal damage to the cartilage and mucosa of
the airways leading to patulous distention and
irregularities of the major bronchi in the field
of irradiation

62. .
• Result in profound damage to the central
airways.
.
• Focal damage to the cartilage and mucosa of
the airways
.
• patulous distention and irregularities of the
major bronchi in the field of irradiation
Radiation therapy

63. CT scan shows dense fibrosis and bronchiectasis
in the radiation field
non–small cell carcinoma of the lung. Pt had
received radiation therapy to the right hilar region
approximately 18 months previously

64. • Cylindrical bronchiectasis is described as
failure of the involved airways to taper
progressively in their distal course.
• Usually, in this condition the bronchial walls
are smooth or regular

65. • ALPHA1-ANTITRYPSIN ANOMALIES
• COPD

66. CLASSIFICATION
• Varicoid bronchiectasis is an allusion to
varicose veins and is marked by irregular
dilation, narrowing and outpouching of the
airways
• Saccular bronchiectasis- also known as cystic
bronchiectasis, includes focal or cystic
distortion of the distal airways

67. • It may be isolated or may be more
confluent,producing the appearance of
bronchiectatic consolidation and volume loss
• Cylindrical bronchiectasis is described as
failure of the
• involved airways to taper progressively in their
distal course

68. A-Cylindrical bronchiectasis with the characteristic signet
ring appearance
B-Varicoid bronchiectasis
C-Cystic bronchiectasis