1
Q
Give an example of a genetic disorders affecting the airways
A
CHARGE syndrome:
Coloboma - Heart defect - Atresia choanae - Retarded growth and development - Genital hypoplasia - Ear anomalies and deafness
2
Q
What are the characteristics of CHARGE syndrome?
A
- 70 % - mutation in CHD7 gene (epigenetic)
- Autosomal dominant
- No family history generally and no significant risk of recurrence
- Management includes interdisciplinary team, follow-up for feeding problems, specific guidelines
3
Q
Give 2 example of a genetic disorder affecting the skeletal system
A
Severe skeletal dysplasia
- Thanatophoric dysplasia
- Achondroplasia
4
Q
What are the characteristics of Achondroplasia?
A
- Detection at the 3rd semester, newborn can live with no cognitive delay
- Gene FGFR3
- Autosomal Dominant inheritance and sporadic (very low risk of recurrence) but the child will have 50% chance to give it to his own children
- Specific guidelines, respiratory symptoms that can be managed by C-PAP at night
LE NAIN DANS GAME OF THRONES
5
Q
What are the characteristics of thanatophoric dysplasia?
A
- Gene FGFR3, but different domain
- At birth- child dies of respiratory insufficiency (lethal skeletal dysplasia)
- Suspicion from 1st trimester (lethal)
- Autosomal Dominant inheritance and sporadic (very low risk of recurrence)
6
Q
Give an example of genetic disorders affecting the muscular system
A
POMPE disease or Glycogenosis type 2 (type of error of metabolism)
7
Q
What are the characteristics of POMPE disease or Glycogenosis type 2 (type of error of metabolism)?
A
- Lysosomal accumulation of glycogen mainly in muscles
- Classical form: 0-3 month old child with hypertrophic cardiomyopathy, severe generalized hypotonia and respiratory dysfunction
- Late onset form, but more a spectrum of presentation, easy to miss !!
- Therapy includes enzyme replacement therapy and has good response (treatable!)
8
Q
What are the 3 ciliopathies genetic disorders affecting the lungs?
A
- Primary cilia
Usually associated with developmental syndromes - Motile cilia (PCD)
- Primary ciliary dyskinesia (PCD)
- Daily lifelong wet cough, chronic recurrent infections, and infertility
- Autosomal recessive or X-linked dominant
= No developmental delay - Nodal cilia
Defects: situs inversus and heterotaxy
9
Q
What is the take-home message of the lecture on respiratory genetic disorders?
A
Include genetic disorders in the differential diagnosis.
Why is that? Genetic diagnosis have an impact on the family (risk of recurrence, counseling, family testing, pregnancy management) and is sometimes treatable!
10
Q
What are the lung-related disease more prevalent in the Indigenous communities?
A
- TB: Prevalent and increasing among the Inuit, 20% of all TB rates in Canada
- Asthma: Higher in adult
- Bronchiolitis: Increased rates among Inuit babies
- COPD: Overall higher prevalence among all indigenous, first nations and Inuit ++, more visits of ER
- Lung cancer: Highest prevalence in the world, tobacco ++
11
Q
What are the lung-related disease decreased among Indigenous communities?
A
- Cystic fibrosis
- Asthma in CHILDREN
12
Q
What are the principal social determinants explaining the high prevalence of lung-related diseases among Indigenous communities?
A
- Housing: can’t own home because of the Indian act, ventilation, humidity
- Overcrowding
- Smoking: infections, CO2 in the house
- Access to care
- Trust
13
Q
What can we do as doctors to adress the social determinants of lung-related diseases among the Indigenous communities?
A
- Make sure you do a thorough Social History to make sure you know the living conditions of your client
- Ask if anyone at home has a chronic cough
- Write a letter for your patient to request a change of home if you think housing is part of the problem
- Become an advocate for Indigenous peoples
- Advocate for vaccination
- Realize that smoking may be a consequence of other social determinants of health
- Very difficult – discuss risks of smoking in culturally sensitive fashion
- Offer smoking cessation treatments and/or programs; covered by NIHB
- Start smoking prevention early (< grade 6)
- Long term interest for working with indigenous people
14
Q
On what type of receptor the ß-agonist acts on?
A
Most B-agonist bind to Gs coupled proteins. Their receptors change shape when bound (GDP to GTP) and then the G proteins are going to act on the production of cAMP, who inhibits LMCK leading to relaxation of airways.
15
Q
On what type of receptors the cholinergic drugs act on?
A
The muscarinic receptors are Gq-coupled and depend on calcium to activate protein kinase. Cholinergic signalling activates MCLK activity, which bronchoconstric the airways.
16
Q
Name the SABAs drugs
A
- Salbutamol (Ventolin)
- Albunerol (Ventolin)
- Isoprenaline
- Terbutaline
- Epinephrine
17
Q
Name the LABAs drugs
A
- Salmeterol
- Formoterol
18
Q
Name the ICS drugs
A
- Fluticasone
- Budesonide
- Cortisol
19
Q
Name the anti-muscarinic drugs
A
- Ipratropium
- Tiotropium
20
Q
Name a specific drug that inhibits of cAMP and its side effects
A
Drugs: Methylxanthines (theophylline)
Side effects: Tachycardia, anxiety, nausea, seizures, hypercalcemia
21
Q
Name a drug that inhibits cell granulation and its side effects
A
Drug: Sodium chromoglycate (chromolyn)
Side effects: Nausea, drowinesss
22
Q
In what order do we give the medication for asthma?
A
ICS –> LABAs –> LAMAs
23
Q
In what order do we give the medication for COPD?
A
LAMA –> LABAs –> ICS
(l’invarse de l’asthme)
24
Q
What are the side effects of SABAs and LABAs
A
- Bronchospasm
- Tremor
- Tachycardia
- Prolonged QT interval
- Hyperglycemia
- Hypokalemia
- Tolerance
25
What are the side effects of ICS?
* Oral candidiasis
* Growth inhibition
* Decreased bone density
26
What is Leukotriene?
A drug that bronchodilates, acts on mucous gland secretion, leukocyte infiltration and bronchovascular leakage
Adverse effect: Liver inflammation
27
What are the 4 pathologic pattern of forms of pneumonia?
1. Nodular (granuloma)
2. Diffuse parenchymal (lobar)
3. Patchy parenchymal
4. Interstitial
28
What are the characteristics of Nodular (granuloma) pneumonia?
**Microscopic appearance:**
Activated macrophages, granular necrosis surrounded by activated macrophages, organisms in the necrotic material (controlled but alive)
**Macroscopic appearance:**
Caveating necrosis (increases development and contagiousness), fibrosis (fibrous capsule, contains TB, but bacteria still alive), caseous necrosis (soft cheese) and old calcified necrosis (hard) often in the upper lobe (apex)
**_TB IS A FORM OF NODULAR PNEUMONIA_**
29
What are the characteristics of diffuse paremchymal (lobar) pneumonia?
**Microscopic appearance:**
Fluid and few inflammatory cells, progress and we can see neutrophils
**Macroscopic appearance:**
Starts in the bottom of the lung, lot of fluid that cause consolidation. Can invade the whole lung (thus LOBAR pneumonia), fibrosis
**_STREPTOCOCCUS PNEUMONIA IS A TYPE OF DIFFUSE PAREMCHYMAL PATHOLOGIC PATTERN_**
30
What are the characteristics of patchy parenchymal pneumonia?
**Microscopic appearance:**
Necrosis
**Macroscopic appearance:**
Patchy, starts in the periphery, abscess with necrosis, empyema (pus)
**_BRONCHOPNEUMONIA IS A TYPE OF PATCHY PAREMCHYMAL PATHOLOGIC FEATURE_**
31
What are the characteristics of interstitial pneumonia?
**Microscopic appearance:**
Diffuse alveolar damage
**Macroscopic appearance:**
Diffuse parenchymal interstitial inflammation
**_CYTOMEGALOVIRUS IS A TYPE OF INTERSTITIAL PNEUMONIA_**
32
What is pneumonia and how is it transmitted?
Pneumonia is an infection of the lung typically involving alveolar space and parenchyma. It is classified by organism (bacterial, virus, typical and atypical), pathogenesis (community acquired, hospitalized, aspiration, ventilation) and by anatomical distribution (lobar, multifocal, bronchoor interstitial).
**Transmission:**
* inhalation
* aspiration
* direct extension
* exogenous contamination
* haematogenous spread
33
What is the pathogenesis of pneumonia?
_1. Defect on host defense_
+
_2. Overwhelming bacterial inoculum_
+
_3. Highly virulent microorganism_
= pneumonia
34
What are the different types of pneumonia?
1. **Bacteria**
* _Typical_: streptococcus pneumonia (most common, specific symptoms, extreme ages at risk)
* _Atypical_: mycoplasma pneumonia (mild, young healthy adults, interstitial pattern)
* _Selected populations_ (SUPER INFECTIONS AKA RESITANCE):
1. Staphylococcus aureus
2. Pseudomonas aeruginosa
1. **Viruses**
* Influenza
1. **Fungus**
35
What syndrome is associated with pneumonia?
Aspiration pneumonia:
* vomit
* seizures
* gram negative and anaerobes bacteria
* smells terrible
36
What are the risk factors of pneumonia?
**Compromised host defence:**
* Impaired swallowing
* Altered mental status
* Immune deficiency
* Ciciliary dyskinesia
* Cystic fibrosis
* Trauma
* Smoking
* Endotracheal tube
Others
* Older age
* Influenza
* Comorbidities
* Structural abnormality
37
What is the most common type of pneumonia (peu importe le setting)?
S. Pneumonia
38
On what is based the diagnosis of pneumonia?
**Symptoms and signs**
* Cough
* Fever
* Dyspnea, pleuritic chest pain
* Myalgia, malaise, fatigue
* Atypical symptoms in older patients: mental status (confusion), falls, loss of appetite, failure to thrive
* Tachypnea, hypoxemia, cyanosis
* Use of accessory respiratory muscles
**Patient risk factors**
**Physical examination**
* Crackles, wheezing, dullness to percussion
**Bood work**
**Microbiology**
* Sputum
**CXR**
**Other dx tests** (ex. CT chest in select cases)
39
What are the possible complications of pneumonia?
* Empyema
* Abscess
* Lung collapse
* Pleural effusion (we analyse a sample of it, indicator is the pH)
40
How do we treat pneumonia?
**Antibiotics** are only for bacteria. Take home messages for the choice of antibiotics:
* We choose an antibiotic that will cover the suspected bacteria (different classes cover different bacteria, many do not cover pseudomonas and atypical bacteria)
* Side effects, types (oral, intravenous)
* Risk of resistance
Other treatments include: drainage, hydration, oxygen and prevention (vaccines, smoking cessation, transmission, aspiration)
41
What is the main factor of poor housing ?
Lack of maintenance is the main factor of water damage and molds
42
Are mold always visible?
NO. They are sometimes invisible but have effect on health so don’t wait for visible molds or disease to act
43
What cause poor housing conditions (molds, coquerelles, rats)?
Various diseases: rhinitis, rhinosinusitis, asthma, cough, wheezing, dyspnea, respiratory infections, conjunctivitis, COPD exacerbation, insomnia, pneumonitis, ear problems, eczema, fatigue, mental health problems
44
How do you assess poor housing conditions with a patient?
1. History of the building and the apartment
2. Visual inspection (outside and inside)
3. Infrared camera: scan large areas and detect abnormal thermal patterns which must be checked with a moisture detector
4. Openings in suspected areas
5. Sometimes, analyses molds, bacterias, bulk or air samples (not the most important test)
45
When should you suspect that the respiratory disease (or other disease) of your patient is due to poor housing conditions?
* Variation in symptoms and disease according to time and place
* More than one person in the household or building are affected in a similar way
* Health problem which aggravates or persists without obvious reason
* Persistent problem of unknown origin, multiple MD visits
* De novo asthma or rhinitis, especially among an adult or an elderly person
46
What are the basic principles of HPA axis?
Based on a mechanism of stimuli and feedback
* HPA axis is regulated by circadian cycle and stress
* Most hormones are not release continuously; they are release by little peaks (pulsatile stimuli)
* Neuropeptides are precursors of proteins
47
What are the basic mechanisms of glucocorticoids synthesis and action?
* As you move from the outside to the inside of the adrenal gland, different hormones are made
* All steroid hormones are derived from cholesterol
* Corticosteroids are lipophilic (hydrophobic) therefore pass trough the cell membranes
* ACTH increases transport of cholesterol to inner mitochondria which will eventually become cortisol
* Corticosteroids have pleiotropic effects: maintain blood glucose, feedback regulation, lipolysis of adipose tissue, catabolic/anti-anabolic effects in bone, immune function and inhibits inflammation (therapeutic effects). Excess corticosteroids leads to Cushing’s syndrome (moon face, developmental delay, poor wound healing)
* _You can’t just STOP taking corticosteroids medication, you have to wean them_
48
Name the 2 big principal disorders of hypothalamic-pituitary-adrenal (HPA) axis
1. Addison’s disease OR crisis: autoimmune, muscular weakness, low PB, depression, weigh loss OR due to abrupt withdrawal of corticosteroid medication
2. Cushing's syndrome: too much corticosteroids leading to moon face, weight gain, poor wound healing
49
Define EBM?
The 3 elements together:
1. Clinical Expertise
2. Evidence (research)
3. Patient preference
50
What are the 3 basic questions need to be addressed for any study:
1. Are the results valid?
2. What are the results?
3. Can I apply the results to my patient?
51
What are the steps of EBM?
1. Ask an answerable question
2. Acquire the available evidence
3. Appraise
4. Apply: Shared decision making / Informed decision making / Paternalistic decision making
5. Evaluate the result (final step added by the librarian madame)
52
A patient comes to see you and asks: “Doctor is that therapy/drug good?” What do you answer?
“(Bitch,) **WHAT’S THE EVIENCE**?”
53
What are the 2 etiologies of bronchiectasis?
1. Infection (ex. TB, funga, immunodeficiency)
2. Impaired drainag (PCD, CF, tumour)
54
What is bronchiectasis and how do you treat it?
Bronchiectasis is a condition in which an area of the bronchial tubes is permanently and abnormally widened (**DILATED**), with accompanying infection (**PUS**).
Treatment:
* Antibiotic
* Bronchodilators
* Bronchopulmonary draingage (chest physio)
* RARE surgery
55
What is cycstic fibrosis?
One of the most common lethal inherited autosomal recessive disorders; it alters the function of **chloride channel**. This results in abnormalities in the **fluid lining the airway surface.**
## Footnote
**Defective gene --\> defective CFTR--\> decreased secretion and ion transport --\> increased water absorption --\> bronchial obstruction --\> inflammation --\> BRONCHIECTASIS**
56
What are the clinical manifestations of cystic fibrosis?
**EXOCRINE ORGANS ARE INVOLVED**
* **Respiratory tract** : persistent sinopulmonary infections and chronic bronchitis with bronchiectasis
* **Pancreatic** insufficiency: vitamins, malnutrition, fatty stools
* **Gastro-intestinal**: meconium ilieus (bowel obstruction)
* **Liver**: bile is thicker = focal biliary cirrhosis
* **Reproductive organs**: infertility
* **Glands**: elevated sweat chloride levels (my baby tastes salty)
57
What are the occupational respiratory disease covered by Quebec's occupational health compensation system (CNESST)?
* Asbestos: asbestosis, diffuse pleural thickening, lung cancer, mesothelioma
* Hard metal disease
* Siderosis
* Silicosis
* Talcosis
* Byssinosis
* Extrinsic allergic alveolitis
* Asthma (if related to work)
This list has not been altered (RADS, silica and cancer...)
58
How do you proove causality between respiratory disease and occupation?
Complete occupational history:
* What kind of work do you do?
* What work have you done in the past?
* Type of work, type of industry, specific company names, manufactured products
* What you did, not just title...
* What were you exposed to, directly or by other workers?
* What protection/precautions were used?
* Other workers developed illnesses?
REMEMBER:
* Almost all respiratory syndromes may have an occupational cause or link
* Many cases go unrecognized for years, may never be discovered, and may never be presented to CNESST
* It is the role of the physician to explore possible links, primarily by a detailed history of all jobs and exposures, along with a suspicious inquisitive mind...
* It is easy to present your patient to the CNESST for a detailed assessment
59
What are the 3 majors respiratory diseases related to occupation + characteristics?
1. Asbestos
Pleural plaques, effusions, asbestosis, MESOTHELIOMA
2. Asthma
Post work (not there before)
3. Silicosis
Nodules
60
What are the grades of dyspnea?
1: Dyspnea with strenuous exercise
2: When hurrying or walking up a slight hill
3: Walks slower than contemporaries on level ground because of breathlessness, or stops for breath when walking at own pace
4: Stops for breath after walking about 100m or a few minutes on level ground
5: Too breathless to leave the house, or when dressing or undressing
61
What is the #1 best pharmacologic treatment for END OF LIFE dyspnea?
Opiates (direct effect on **perception** and **dyspnea).**
Dosing:
* **Pain: 5-10mg** po q4h (mouth, every 4 hours)
* **Dyspnea: 0.5-1** mg po BID
62
What are the treatments for NOT end of life dyspnea?
1. Reassurance
2. Education
3. Guidelines treatment for the diagnosis
**Curative dominates (treat cause) but palliative care can occur at the same time (treat symptoms)**
