Review of Bronchiectasis and Pulmonary Hypertension

1. Bronchiectasis
Jamal Turki, M.D
American Board Internal Medicine
American Board Pulmonary Medicine
American Board Critical Care Medicine

2. Bronchiectasis
• Definition: An acquired disorder of the major bronchi and
bronchioles that is characterized by permanent abnormal
dilatation and destruction of bronchial walls.
• Requires 2 Factors:
– An infectious insult +
– One of the following:
• Impairment of drainage
• Airway obstruction
• &/or Defect in host defense

5. Morphological types
• Cylindrical or tubular bronchiectasis
• Varicose
• saccular or cystic bronchiectasis

6. Bronchiectasis: Etiology
• Localized:
– Airway obstruction: FB (Rt lung), Tumor, Mucoid impaction
• Diffuse:
– Cystic fibrosis: most common
– Defective host defenses
– Rheumatologic diseases: RA, Sjogren’s syndrome
– Post-Pulmonary infections: Viral, Mycoplasma, Measles, Pertussis,
TB, MAC
– Allergic Broncho-Pulmonary Aspergillosis (ABPA)
– Dyskinetic cilia syndrome / Kartagener’s syndrome
– Young's syndrome

7. Defective host defenses
• Agammaglobulinemia
• HIV
• Chronic granulomatous disease
• Hypogammaglobulinemia: childhood with repeated
sinopulmonary infections
• Isolated IgG subclass deficiency: (NL total IgG)

8. Pulmonary infections
• Viral or Mycoplasma infection
• Tuberculosis
• Childhood whooping cough (Pertussis)
• Mycobacterium avium complex (MAC)
• Infections in patients with bronchiectasis: Usually caused by:
Hemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae

9. Allergic bronchopulmonary aspergillosis
• Should be suspected in patients with a long Hx of asthma that is
resistant to bronchodilator therapy and associated with a cough
• ABPA probably represents a hyperimmune reaction to the Aspergillus
organism rather than a true infection
• Blood eosinophilia, very high plasma IgE levels, and precipitating and
specific antibodies to Aspergillus

10. Symptoms:
• Cough,
• Chronic daily sputum production.
• Hemoptysis
• Dyspnea
• Rhinosinusitis
• Recurrent pleurisy
• Wheezing

11. Physical findings
• Crackles
• Wheezing
• Digital clubbing

12. Diagnosis
• Clinical + Radiographically
– Clinical: chronic daily cough with viscid sputum production
– X-Ray: Bronchial wall thickening and luminal dilatation on chest
CT- scans

13. Diagnosis
• CBC + Diff
• Ig quantitation: levels of the immunoglobulins IgG, IgM &
IgA
• IgG subclasses
• Sputum smear & culture for bacteria, Mycobacteria, &
fungi
• Rheumatoid factor

14. Diagnosis
• PFT:
– NL if localized
– Obstructive defect with hyperinflation, decreased Dlco
– + Restrictive defect
• Bronchoscopy: Mucosal biopsy (ICS), cultures (focal infections)
• Sweat chloride test analysis (CF)

15. Diagnosis: CXR
• CXR:
– Linear atelectasis
– Dilated and thickened airways
– Irregular peripheral opacities

16. Ct/cxr

17. Diagnosis: HRCT
• HRCT: Airway dilatation:
– Parallel “tram track” lines
– “Signet ring” shadows: A
luminal airway diameter >
1.5 x the adjacent vessel.
– Small nodular opacities:
"tree-in-bud” pattern

18. Ct/cxr

19. Acute exacerbation of bronchiectasis
• Change in sputum production (amount / color)
• Increased dyspnea
• Increased cough
• Fever
• Increased wheezing
• Malaise, fatigue, or lethargy
• Decreased exercise tolerance
• Changes in chest sounds
• Reduced pulmonary function
• Radiographic changes consistent with a new pulmonary process

20. Acute exacerbation of bronchiectasis
• Colonizing bacterial flora includes:
– Hemophilus influenzae,
– Pseudomonas aeruginosa,
– Streptococcus pneumoniae: less frequent

21. Treatment
• Treat Infections: (cornerstone)
– Antibiotics: Fluoroquinolone
– > 10 days duration
– ? Role of AB for infection prevention
– If Pseudomonas : 2 class (combined) anti-pseudomonal AB
– If MAC: combined Rx for ~ 12-18 months

22. Treatment
• Bronchial Hygiene:
– Hydration and mucus clearance: mucolytic agent acetylcysteine
(Neb). ? aerosolized recombinant DNAse (good for CF)
– Bronchodilators: β-agonists + Anti-cholinergics
– Anti-inflammatory Rx: Corticosteriods & NSAID
– Physiotherapy: Chest percussion 3-4 /day
– Pulmonary Rehabilitation

23. Bronchopulmonary Hygiene
• removal of respiratory secretions is
beneficial
• chest percussion and postural drainage
• chest clapping or cupping
• inflatable vests or mechanical vibrators
• Oral devices that apply positive end-
expiratory pressure maintain the patency
of the airway during exhalation

24. Surgery
• Localised bronchiectasis
• Proximal obstructive lesion
• Massive hemoptysis
• Recurrent infections with resistant m.o

25. Pulmonary Hypertension
Jamal Turki, M.D

26. Definitions
Pulmonary hypertension is an elevation in pulmonary
vascular pressure caused by an isolated increase in
pulmonary arterial pressure or by increase in both
pulmonary arterial and pulmonary venous pressure.
Pulmonary arterial hypertension refers to a sustained
elevation of mean pulmonary arterial pressure to greater than 25
mmHg at rest or more than 30 mmHg during exercise, with
normal pulmonary capillary wedge pressure and left ventricular
end-diastolic pressure (<15 mm Hg) .

27. Diagram of Pulmonary and Systemic Circulation

28. Primary Pulmonary Hypertension
An estimated of 500 – 1000 new cases are diagnosed annually.
There is an incidence of about 2-3 per million per year and a
prevalence of 15 per million.
This disease can occur in men, women and children of all ages.
However, it is most common in females between 20 and 40 years
old, with twice as many cases reported in women then men.
The condition is rare in children but is sometimes seen in infants
born with heart defects. Pulmonary hypertension may be a primary
or secondary cause of hypoxia in neonates.

29. Ordinarily, blood vessels in the lungs provide less resistance to blood
flow than blood vessels in the rest of the body do. Hence, blood
pressure is usually much lower in the lungs. While pressure in
general circulation is about 120/80 mm Hg, in the pulmonary arteries,
it is only around 25/15 mm Hg.
Mean (average) pulmonary artery pressure
= number between highest and lowest pressures
Normal
at rest : 14 mm Hg
Pulmonary hypertension
at rest : 25 mm Hg
during exercise : 30 mm Hg

30. Significance of Pulmonary arterial hypertension
Pulmonary arterial hypertension is the third cause of CHF
The median survival was 2.8 years with an estimated 5-year
survival of 34%.
---NIH Registry. Ann Intern Med 1991; 115: 343-349

31. Annual number of hospitalizations among persons
with pulmonary hypertension, United States, 1980–
2002
CDC, National Hospital Discharge Survey.

32. WHO Classification of pulmonary hypertension
Group 1. Pulmonary artery hypertension (PAH)
1.1 Idiopathic (IPAH)
1.2 Familial (FPAH)
1.3 Associated with (APAH)
1.3.1 Collagen vascular disease
1.3.2 Congenital systemic-to-pulmonary shunts
1.3.3 Portal hypertension
1.3.4 HIV infection
1.3.5 Drugs and toxins
1.3.6 Other (thyroid disorders, glycogen storage disease, Gaucher disease, splenectomy, hereditary haemorrhagic telangiectasia,
haemoglobinopathy)
1.4 Associated with significant venous or capillary involvement
1.4.1 Pulmonary veno-occlusive disease
1.4.2 Pulmonary capillary haemangiomatosis
1.5 Persistent pulmonary hypertension of the newborn
Group 2. Pulmonary hypertension with left heart disease
Group 3. Pulmonary hypertension associated with lung disease and/or hypoxaemia
Group 4. Pulmonary hypertension due to chronic thrombotic and/or embolic disease
Group 5. Miscellaneous (sarcoidosis, histiocytosis X, lymphangiomyomatosis, compression of
pulmonary vessels)
(Venice 2003; revised from Evian 1998)

33. Histopathology
1. Severe concentric laminar intimal fibrosis
2. Medial hypertrophy
3. in situ thrombosis of the small residual lumen
intima media
Main vascular changes
of PAH
• Vasoconstriction
• SMC and endothelial-
cell proliferation
• fibrosis
• thrombosis

34. Pathophysiology
Imbalance of vascular effectors
Perturbations in the normal relationships between
vasodilators and vasoconstrictors,
growth inhibitors and mitogenic factors,
antithrombotic and prothrombotic determinants.
Pulmonary endothelial-cell dysfunction or injury
(Endothelin-1,Nitric Oxide and prostacyclin pathway)
Stimuli: shear stress, Po2, Viruses (HIV, HHV-8)
Autoimmunity (CREST,SLE), Drugs
Main vascular changes of PAH
Vasoconstriction
SMC and endothelial-cell proliferation
fibrosis
thrombosis
Intrinsic
susceptibility
(PPH-1,BMPR2,Kv)

35. Abnormally high BP in pulmonary arteries
Increased pressure damages large and small pulmonary arteries
Blood vessel walls thicken
Cannot transfer oxygen and carbon dioxide normally
Levels of oxygen in blood fall
Constriction of pulmonary arteries
Further increase in pressure in pulmonary circulation

36. Pulmonary Hypertension
right side of heart must work harder push blood through
pulmonary arteries to
lungs
right ventricle thickens
and enlarges
cor pulmonale
Heart Failure
In some patients Polycythemia
Leads to Pulmonary Embolism

37. Pathophysiology
-PVR limits RV SV and the volume for LV filling
-LV compressed by intraventricular septum during systole,  LV
volume/filling, CO/BP
-BP leads to coronary perfusion which can lead to myocardial
ischemia/R sided failure
-coronary blood flow to RV usually occurs during diastole and systole
but is decreased if RV pressures are equal to or higher than
systemic pressures
-hypoxemia from CO/pulm blood flow or from R to L intracardiac
shunt (if RA pressures higher than LA)

39. Functional Classification
A. Class I- Patients with pulmonary hypertension but without resulting
limitation of physical activity. Ordinary physical activity does not
cause undue dyspnoea or fatigue, chest pain, or near syncope.
B. Class II- patients with pulmonary hypertension resulting in slight
limitation of physical activity. They are comfortable at rest. Ordinary
physical activity causes undue dyspnoea or fatigue, chest pain, or
near syncope.
C. Class III- patients with pulmonary hypertension resulting in marked.
Limitation of physical activity. They are comfortable at rest. Less
than ordinary activity causes undue dyspnoea, fatigue, and chest
pain or near syncope.
D. Class IV -patients with pulmonary hypertension with inability to carry
out any physical activity without symptoms. these patients manifest
signs of right heart failure. Dyspnoea and /or fatigue may be present
even at rest. Discomfort is increased by any physical activity

40. History
Exertional dyspnea
Fatigue or weakness
Peripheral edema and/or ascites
Angina
Near syncope or syncope
“An impressive feature … was the contrast between the appearance of good
health when at rest and the striking discomfort evoked by even mild exertion.”
------ original clinical description by Dr. David Dresdale, 1951

41.  shortness of breath (dyspnea)
Initially, only short of breath when exert oneself physically but
eventually may be short of breath most of the time, even when
at rest.
 fatigue or light-headed upon exertion
 dizziness or fainting spells (syncope)
 swelling (edema) in ankles, legs and eventually in
abdomen (ascites) – fluid leak out of veins and into tissues
 bluish colour to lips and skin (cyanosis)

42. Physical Examination
Cardiovascular findings:
Large a wave in the jugular venous pulse;
Prominent v waves in the jugular venous pulse
Low-volume carotid arterial pulse with a normal upstroke;
Left parasternal (right ventricular) heave;
Systolic pulsation in the second left intercostal space;
Ejection click and flow murmur in the second left intercostal space;
Closely split second heart sound with a loud pulmonic component;
Fourth heart sound of right ventricular origin
Third heart sound of right ventricular origin
High-pitched early diastolic murmur of pulmonic regurgitation,
Holosystolic murmur of tricuspid regurgitation
Signs of right ventricular failure (hepatomegaly, peripheral edema, and
ascites)
Cyanosis
Patients whose PAH is associated with another illness often
have clinical features of that disease.

43. Chest Radiography
Enlargement of the main pulmonary artery and its major
branches, with marked tapering of peripheral arteries .
The right ventricle and atrium may also be enlarged.
In contrast to the plethoric peripheral lung fields in patients
with left-to-right shunts, oligemia is noted in these lung
regions in patients with PAH.
Encroachment of the retrosternal air space on the lateral
film -- right ventricular enlargement/hypertrophy

44. CXR-PA view
Enlargement of the main pulmonary artery and its major
branches, with marked tapering of peripheral arteries .

45. CXR-lateral view
Encroachment of the retrosternal air space -- right ventricular
enlargement/hypertrophy

46. CXR-PA view
The right ventricle and atrium may also be enlarged.

47. ECG
• Highly specific
but not very
sensitive.
• Right axis
deviation
• Right atrial and
right ventricular
enlargement.
• Right bundle
branch block
• ST and T wave
changes in the
anterior
precordial leads.

48. ECG
Highly specific but not very sensitive.
Right atrial and right ventricular
enlargement.
Right bundle branch block
ST and T wave changes in the anterior
precordial leads.

49. Echocardiography
Enlargement of the right atrium and ventricle with
normal or small left ventricular dimensions.
Abnormal septal motion as a result of the right
ventricular volume and pressure overload.
Delayed opening of the pulmonic valve, midsystolic
closure, and an increase in the ratio of right
ventricular pre-ejection time to total ejection time.
Doppler echocardiographic quantitation of right
ventricular systolic pressure may be obtained by
measuring the velocity of the tricuspid regurgitant jet
and using the Bernoulli formula.
PAP = 4 x velocity2 + RAP

50. Pulmonary Function Tests
Usually completely normal for PPH
Vital capacity may be reduced to approximately
80%
Hyper-reactivity of the bronchial tree is common,
which can lead to a misdiagnosis of asthma
Diffusing capacity for carbon monoxide (DLCO) is
mildly reduced to approximately 60 to 80%
Presence of arterial hypoxemia is due to V/Q
mismatch and/or reduced mixed venous oxygen
saturations resulting from low cardiac output

51. Right heart Catheterization
The diagnosis of PAH cannot be confirmed
without right heart catheterization (gold
standard)
patients with PAH should have a low or
normal pulmonary capillary wedge
pressure

52. Exercise Test – 6MWT
The 6-minute walk test (6MWT) is recommended
as a standard exercise test by American
Thoracic Society
Healthy subjects’ 6MWDs: 400 to 700 m and it
varies.
It is commonly used for :
Before-and-after treatment comparisons
Measuring functional status
Predicting hospitalization and death

53. Acute Vasoreactivity Test
The test: using right-heart catheterization to measure
pulmonary arterial pressure when challenged with
vasodilators ( adenosine IV, or Epoprostenol IV, or NO
inhale)
A positive response is considered when there is a greater
than 10 mmHg reduction in mean pulmonary artery
pressure, to a mean pulmonary artery pressure of less
than 40 mmHg.

55. Clinical Assessment
H & P
6MWT

56. Treatment -- General measures
Physical activity and lifestyle changes
• Counseling
• Cardiopulmonary rehabilitation program
• Graded exercise activities: bike riding and swimming -- safe
• Isometric activities: lifting weights or stairclimbing – presyncope or
syncope
• Young women: birth control

57. Rubin, L. J. et. al. Ann Intern Med 2005;143:282-292
Potentially Hazardous Activities for Patients with Pulmonary Arterial
Hypertension

58. Treatment -- General measures
Supplemental oxygen
To keep O2Sat > 90%
Nocturnal desaturation may occur in patients with pulmonary
hypertension, even in the absence of daytime hypoxemia or
sleep-disordered breathing. Some experts suggest an
assessment of noctural oximetry in patients with pulmonary
hypertension in order to determine whether nocturnal
supplemental oxygen therapy is indicated to maintain
satisfactory oxygen saturation during sleep. --- Lewis J. Rubin,
2004

59. Calcium Channel Blockers
 blocks entry of calcium into muscle cells of heart & arteries
 improve ability of heart to pump blood
 relaxes smooth muscle in walls of heart and blood vessels
 amlodipine , diltiazem, nifedipine , nicardipine etc.
 only small number of people with PH respond to them
 side effects – constipation, nausea, headache, rash, edema,
drowsiness, dizziness, low blood pressure

60. Blood Vessel Dilators
Prostacyclin
 substance that acts like a hormone (prostaglandin)
 imitates behaviour of natural prostacyclin
 powerful vasodilator and anti-clotting agent
 prevent blood clots from forming
 given intravenously through catheter
 bridge to help those waiting for transplant
 Epoprostenol - 1st vasodilator approved by FDA
 Ilopost - inhaled through nebulizer
 Treprostinil - injected under skin
 side effects - jaw pain, nausea, leg cramps etc
 need comprehensive follow-up care

61. Endothelin Receptor Antagonists
 available in pill form
 reverse effect of endothelin (blood vessels constriction)
 Bosentan - may improve stamina of people with PH
 not for pregnant women
 need monthly liver monitoring - risk of liver complications
Phosphodiesterase Inhibitors
 Sildenafil - Viagra
 blocks the enzyme phosphodiesterase
 accentuates actions of nitric oxide
 opens blood vessels in the lungs - dilation
 side effect - vision problems

62. Anticoagulant
 warfarin
 prevent formation of blood clots within pulmonary arteries
 risk of bleeding complications –
 periodic blood tests
 more than 100 drugs can interact with anticoagulants
Diuretics
 eliminate excess fluid from body
 reduces amount of work heart has to do
 limit fluid buildup in the lungs
 improve exchange of gases in lungs

63. Oxygen
 oxygen therapy
 especially for those who live in high altitude
or have sleep apnea
 continuous use of oxygen through
nasal prongs/oxygen mask
 relieve shortness of breath
Cardiotonics

64. Transplants
 surgical interventions – considered only in extreme cases
 treatment for severe secondary PH if treatment of the underlying
disorder fails
 surgically replace damage organs with healthy donated organs
 lung and/or heart transplantation
 most common : single-lung transplant, fewer complications than
double-lung or heart-lung transplant
 lung transplant - improvement in structure and functioning
of right ventricle
 major risks : rejection of transplanted organ, serious infection
 take immunosuppressant drugs for life – help reduce chance of
rejection
 survival rate is about 60% per year and 37% per 5 years

65. Treatment algorithm for
pulmonary arterial hypertension

66. THANK YOU