Lecture 16: Combination of restriction and obstruction

Question 1

What is the cause of sarcoidosis?

Answer 1

An (antigen) particle is inhaled

In the lung it is loaded onto a MHC-II complex (of an antigen presenting cell, aka APC). The lung is full of APCs, such as dendritic cells, on surveillance for microbes

Receptors on CD4+ T cells bind to antigen

APCs and antigen-bound T cells release cytokines

These activate macrophages which organize into granulomas

Granulomas also occur in TB and fungal infections, but in sarcoidosis they are sterile

Question 2

How do you diagnose sarcoidosis?

Answer 2

A biopsy demonstrating granulomas is needed

Question 3

What are the different clinical presentations of sarcoidosis?

Answer 3

Bilateral hilar lymphadenopathy

Small nodules in the lymphatic tracts in the lungs

CNS disease

Uvelitis, parotitis

Heat block, arrhythmia, heart failure

Skin nodules

Erythema nodosum

Question 4

What are the systemic symptoms of sarcoidosis?

Answer 4

Fatigue
Sweats
Weight loss
Fevers
Generalised achiness

Question 5

What are the symptoms of pulmonary sarcoidosis?

Answer 5

Cough
Dyspnea with exertion
Chest tightness

Question 6

What may be caused by chronic inflammation?

Answer 6

Fibrosis

Question 7

What pharmaceutical treatments are available?

Answer 7

Systemic corticosteroids (eg. prednisolone), +/- other immunosuppressant medications

Question 8

What should be included in a screen for multi-organ disease?

Answer 8

Eye exam
EKG
Blood tests for blood cell counts
Liver function
Kidney function
Calcium

Question 9

What is cystic fibrosis?

Answer 9

Autosomal recessive disease

Mutation of cystic fibrosis transmembrane conductance regulator (CFTR)

Most common genetically inherited disease in Caucasians

CFTR protein: 1480 amino acids - elaborate 3-D shape - ion channel which allow Cl- to cross membrane - H20 passively follows Cl-

Question 10

What is the most common mutation in CF?

Answer 10

ΔF508 (loss of phenylalanine at amino acid position 508)

ΔF508: CFTR protein doesn’t fold properly - gets degraded

Question 11

How many amino acids make up the CFTR protein?

Answer 11

1480

Question 12

How can you diagnose CF?

Answer 12

Genetic testing

Sweat test

Question 13

What are the symptoms of CF?

Answer 13

Excessive mucous, difficult to mobilise

Dyspnoea

Question 14

What are the exam findings in CF?

Answer 14

Wheezing

Rhonchi

Question 15

What are the imaging findings in CF?

Answer 15

Bronchiectasis

Mucous plugging

Hyperinflation young age - shrunken, fibrotic lungs later

Question 16

What is bronchiectasis?

Answer 16

Permanently dilated airways + thickened walls (from scarring and/or chronic inflammation)

Question 17

What are the pulmonary complications of CF?

Answer 17

Acute infections:

• gram positive common in young age - both gram positive and gram negatives in older age
• resistance is a common and BIG problem: MRSA and pseudomonas aeruginosa

Chronic infection:

• pseudomonas and Burkholderia cepacia
• allergic bronchopulmonary aspergillosis (ABPA) from aspergillus growing in the airways

Haemoptysis:
- inflamed blood vessels in bronchiectasis

Respiratory failure:
- infectious insults + progressive loss of lung function from fibrosis

Question 18

What are the airway clearance techniques?

Answer 18

Postural drainage
Chest physical therapy
Percussion vest

Question 19

What is a mucous thinner?

Answer 19

Hypertonic nebulizer treatments

Question 20

What treatment options are available for CF?

Answer 20

Airway clearance techniques

Inhaled bronchodilators

Mucous thinners

Corticosteroids (inhaled > systemic)

Antibiotics

CFTR potentiators (Ivacaftor)

Lung transplant

Pancreatic enzyme replacement (lipase, protease, and amylase)

Question 21

What are the causes of restriction?

Answer 21

ILD
Sarcoidosis
Obesity
Scoliosis
NMD
Pneumonia
TB

Question 22

What are the causes of obstruction?

Answer 22

COPD
Asthma
Bronchiectasis
Cystic fibrosis