resp

Question 1

what are the 6 conclusions of the CTS severe asthma guideline

Answer 1

1. Feno Eo and Ige can be used to phenotype
2. LAMA (tiatrop) can be added if over 12yo and on high dose ICTS/LABA
3. over 6 yo with perenial and on high dose ICS can do omalizumab
4. anti il5 can be used for eo asthma in over 18yo if on high dose and second ocntroller
5. macrolifes dec asthma exac over 18yo
6. bronchial thermoplasty reduced exacerbation but unknown role.

Question 2

define severe asthma

Answer 2

1. patient requiring high dose ICS and second controller x in prev year
2. needed systmeic steroid for 50% of prev year to remain controlled
3. remains uncontrolled despite above therapy.

Question 3

define uncontrolled asthma

Answer 3

as per CTS control criterhia
OR using ACQ >1.5, or ACT <20, or cACT<20

needing steroids 2 or more times for more then three days in prev year

one hospilization or ICU

airflow limitation - after bronchodlaite FEV1 <80% of personal best

Question 4

what is periostin

Answer 4

periostin is a matriculleular and extracellular protein released when il4 and 13 released and role in asthma thought ot be in BM and causing fibrosis of subepithelial level

not useful to measure in children.

Question 5

state if the following useful to follow for xolair and anti il5

serum Eo
sputum Eo
IgE
periostin
feno

Answer 5

serum Eo - useful for anti il5 and xolair for LESS EXACERBATION

sputum Eo helps with anti il5 RESPONDER but not macrolifes

ige not useful in the approved xolair range to identify better benefit and not useful for anti il5 responder

feno not clearily iuseful for responders

Question 6

omalzumb indications in asthma

ige 30-700

Answer 6

over 6 yo with mod-severe persistnet asthma, despite high dose ICS controller therapy that are sneisizied to perrential allergen with ige in 30-700 range, or 1300 if 6-11,

goal: reduce exacerbation, dec ICS dose and pt sx improve

better response if Eo serum >260 and have a hx of freq exacerbation

Question 7

name cut offs for the diff il5 in temrs of Eo

Answer 7

mepo
150 initia, 300 in last year
subcut 100mg q4q

resi
300, IV q4w 3mg.kg

benra
300 subcur q 8w

Question 8

what is bronchial thermplasty

Answer 8

endoscopy using radiofrequency ablation to decrease airway smooth muscle

5% had pnuemonia and atelectasis

but did
dec ATM, dec typr 1 collagen, membrane thickness, neuroendocrine cells

improved QOL, dec exacerbation, dec inhaler use, and safetly for five year

Question 9

name 5 LMW and 5 HMW occupation ashtma agents and their corresponding job - allergic asthma

can get irritant from REACTIVE AIRWAY DYSFUNCTION sydnrome where u get high concentration 1x of some chemical spill and then get asthma

manage - peak flow q2h for 2w, meth choline test there
or GOLD standarant inhalation challenge

change nevt, PPE, ICS, smoking cessation

Answer 9

HMW more ige medaited

• animal protein: vet
• fish/shellfish: seafood worker
• latex: HCP
• flour - baker
• enzyme- baker

LMW non ige medaited
- isocyanates: spray paint
- formaldehyde: HCP
- amine: shellac
- acrylates: nail ppl
- pilatic acid: wood worker
persulfate salt - hardiress hair bleach

Question 10

name4 causes of HP

Answer 10

Farmer lung: thermophillic actinomyces
Bird fancier lung: dropping, serum avian proteins
Malt worker lung: aspergillus fumigatus
Saxophone lung: candida
Hot tub lung: mycobacterium avium complex

Question 11

imaging findings in 3n stages of HP

Ag:ab compled → Complement C5a → macrophages, release cxcl3,5,8, PMN recreuirted → tissue fibrosis –>CHRONIC
Also Ag – th1/th2response get lymphocyte influx → th1 predmoninance ACUTE HP → can lead to CHRONIC
If th2 can inc il4/13 and subacute HP→ CHRONIC

Answer 11

cute: th1, 4-6h,fever chills,non productive cough,tachypnea,spontaneous recovery. Imaging shows normal or fleeting ground glass
Subacute: gradual onset, weeks to months, th2, dyspnea, productive cough, fatigue, anorexia, weightnloss and imaging diffuse micronodules, air trap, mild fibrosis
Chronic: progressive over years, no explsoive sx, cough and sob, clubbing, fibrotic lung with permanent damage, and imaging ground glass, empysema, honeycomb and parenchymal micronodules
Can occur via PMN via complement, can occur via TH1 or TH2

Question 12

diagnosticriteria for HP

Answer 12

diagnostic criteria 
4 major
Hx confirms exposure
Sx worsen with exposure
Precipitin test AND OR BAL >50% lymphocytosis,cd8 predo
CT and CXR findings
BAL lymphocytosis
Histopathology
Natural challenge
2 minor
Dec DLCO
Basilar rales
Arterial hypoxemia with exertion

Question 13

Give HES definition (3) What two immediate mediators do eosinophils release? (2)

Answer 13

Hypereosinophilia defined as:
Peripheral blood absolute eosinophil count of > 1.5x10^9cells/L (or 1500 cells/microL) on at least two occasions at least 1 month apart AND/OR
Pathologic confirmation of tissue hypereosinophilia, defined as:
Bone marrow >20% eosinophils and/or
Infiltration that is extensive in the opinion of a pathologist and/or
Marked deposition of eosinophil granule proteins, demonstrated by immunofluorescence

Hypereosinophilic syndrome is defined as hypereosinophilia (as above) AND evidence of eosinophil-mediated end organ damage (+ other causes for end-organ damage excluded)

Immediate mediators:
Major basic protein, eosinophil cationic protein, eosinophil peroxidase, eosinophil-derived neurotoxin

Question 14

what are preformed mediators in mast cell

Answer 14

histamine, chymase, protease, carboxypeptidase, tnfalpha

15 min pgd2, ltc4, ltd4, lte4, ltbn4

min to days
chemokine
il;3,5,gmcsf
tnf alpha
ccl5 - RANTE
mip1alpjha- ccl3

Question 15

wht r preformed in BASOPHIL

Answer 15

histamine

15min ltc4,ltd4,, lte4

late
days
il3,il4, i;5 il13

Question 16

what r preformed in EOsinophil
\

they makeROS

Answer 16

prumary granule CHARCOT LEYDEN crystals

mbp, cationic protein, peroxidase, neurotoxin, lososomal hydrolases

later
pge2, ltc4,ltd4,lte4

Question 17

What two families of receptors do platelets have? (2) Name 2 mechanisms in how IVIG work in increasing platelet count in ITP? (2)

Answer 17

Integrins (GPIIb/IIIa receptor)
Leucine-rich repeats receptors
Selectins
Tetraspanins
Prostaglandin receptors (eg. thromboxane receptor)
Lipid receptors (eg. PAF receptor)
Immunoglobulin superfamily receptors
Tyrosine kinase receptors

2 mechanisms in how IVIG works in increasing platelet count in ITP:
Blocks Fc receptors on phagocytes in spleen and liver - thus prevent reticuloendothelial uptake of autoantibody covered cells
Neutralization of autoantibodies by anti-idiotype antibodies
Inhibition of antibody production by blockade of CD32 on B lymphocytes

Question 18

List 2 periodic fever syndromes with known mutations and list their mutations. (4). What is the most serious complication these syndromes can give you (4 marks for 1 answer). Name 1 period fever syndrome that can present with urticaria (1).

Answer 18

Familial mediterranean fever: MEFV (encodes pyrin protein)
NOMID, Muckle Wells Syndrome, FCAS: NLRP3 (encodes cyropyrin)
HyperIgD: MVK (mevalonate kinase)
TRAPS: TNFRSF1A (encodes p55TNF receptor)

Most serious complication: renal amyloidosis

1 periodic syndrome that can present with urticaria: FCAS, Muckle Wells, NOMID

Question 19

What is the product monograph range of weight and IgE level for Xolair in use for asthma? (4) What other conditions has Xolair been shown to be effective in, with at least 1 RCT showing? (4)

Answer 19

Uncontrolled on ICS
With sensitivity to a perennial aeroallergen (eg, dust mites, pet dander, cockroach debris)
Aged ≥12 years (**12 as per product monograph, and 6yrs as per CTS guideline on severe asthma)
Total IgE level of ≥30 to 700 IU/mL
Body weight of 66 to 330 pounds (20-150kg)
Dosing is based on a combination of age, IgE level, and body weight. Please see dosing tables in the full Prescribing Information.
Other conditions that Xolair has shown to be effective:
Chronic spontaneous urticaria
Food allergy (eg. increasing the threshold dose in patients with peanut allergy)
Oral immunotherapy (improves efficacy and safety)
Cold Urticaria
Seasonal allergic rhinitis

Question 20

17. A girl has sensitivity to mango peels and also has sensitivity to poison ivy. What is the
    allergen involved? (1)

Answer 20

Urushiol
Although some people can have allergies to the flesh of mangoes, for most it is the mango’s skin.
Mango skin, bark and leaves contain the same toxic substance, urushiol, as in poison ivy.

Question 21

: 4 reasons for persistently poorly controlled asthma (4)

Answer 21

smoking ( first or second hand)
non compliance with meds, poor technique
continued exposure to allergen
wrong diagnosis

Question 22

reoperative anaphylaxis. List 5 reasons (5)

Answer 22

Neuromuscular blocking agents (NMBA) most common in Europe
IgE-mediated or direct mast cell activation
IgE sensitization is believed due to cross-reactive tertiary or quaternary ammonium groups found in both NMBAs and topical cosmetics/personal products and OTC cough remedies (eg. pholcodine)
Hence why allergic reactions to NMBAs can occur w/ initial exposure
Eg. rocuronium, succinylcholine, atracurium, pancuronium, vecuronium

Antibiotics (specifically cefazolin) is the most common in the US
Vancomycin also common (due to direct histamine release from mast cells)

Chlorhexidine
Antiseptic solutions applied to surgical fields (especially mucosal surfaces) and urethral lubricants, some central venous catheters
Found in non-medical settings in toothpastes, antiseptic mouthwashes, bathing solutions, lozenges

Latex
Becoming less common as a culprit for perioperative anaphylaxis, as latex-free environments are more common
Previously, most common sources were: gloves, drains, catheters
Colloids and plasma expanders (eg. dextran, hetastarch, albumin), or gelatin contained in plasma expanders
Role of alpha-gal allergy
Patients sensitized to alpha-gal may report delayed allergic reactions to ingestion of beef, pork, lamb
In perioperative setting, may react to gelatin-based colloids, bovine/porcine heart valves, gelatin in heparin/hemostatic agents
If patient has history of allergic reaction to meat ingestion → avoid use of animal-derived products in OR
Hypnotic induction agents: two kinds → barbiturates (eg. thiopental) and nonbarbiturates (eg. propofol, etomidate, ketamine, benzodiazepines)

Question 23

. What are probiotics (2)? What are two bacteria in normal gut of nonallergic kids (2)? What
does the current evidence say about recommending probiotics for allergy?

“Probiotics” is a general term for different strains/species of micro-organisms with a wide and varying range of clinical/immunologic capacities.
The FAO and WHO have defined probiotics as “live micro-organisms, which when administered in adequate amounts confer a health benefit on the host. The most commonly used probiotics are lactobacilli and bifidobacteria strains.

Answer 23

obiotics are lactobacilli and bifidobacteria strains.

“Beneficial Flora” Include Lactobacillus Acidophilus (Lactobacteria) and Bifidobacterium Bifidum (Bifidobacteria)

Question 24

four risk factors for th2 asthma

Answer 24

maternal smoke
less older sibs
dec childhood infxns
less animan in early life/farm life

Question 25

ozone effect on asthma

Answer 25

Emergency visits and hospital admissions in Ontario in the summer months have been related to ozone and sulphates
Ozone can increase non-specific airway responsiveness
Ozone exposure prior to allergen exposure enhances the allergen airway response
Deisel exhaust can act as an adjuvant and increase IgE production to allergens

Question 26

name example of

non caseating
caseating
and
necrotizing granuloma disease

Answer 26

1) non-caseating: sarcoidosis, Crohn’s, H. Pylori, HP, GLILD, CGD
2) caseating: TB, atypical mycobacterium, histoplasmosis (or CGD granulomaa from fungi)
3) necrotizing: GPa, EGa, RA

Question 27

What 5 features suggest a diagnosis of asthma in a 3-year old you’re seeing in your clinic who’s on low dose ICS x2 months and beta agonists PRN?

Answer 27

Documentation of airflow obstruction (eg. what prompted them to start therapy → wheeze?)
Response to ICS
Reversibility documented with physician with SABA
No other causes (ie, no foreign body)
Atopy

Note from Amiirah: I think we should add as three of them as CTS preschool guideline states this as adquate response to ICS:
50% fewer moderate/severe exacerbations,
shorter and milder exacerbations
fewer, milder symptoms between episodes.

Question 28

egpa bx of lung shows what?

Answer 28

gold standard is lung bx showing the eo infiltrate and allergic granuloma and necrotizing vasculitis

Question 29

fungal disease of lung classification

Answer 29

Types of lung disease caused by aspergillosis:
ABPA - see below
Asthma with aspergillus sensitization - one or more ABPA criteria but does not meet full criteria
Aspergilloma: a fungus ball made of hyphae, fibrin, mucus and cellular debris. It arises within preexisting pulmonary cavities that have become colonized with Aspergillus. Often it is stable, and patient has few symptoms (eg. mild cough). Diagnosed by: radiologic evidence of a rounded mass in a pulmonary cavity + evidence of aspergillus (either positive sputum or IgG)
Aspergillus nodule(s): occurs in immunocompetent hosts, can have single or multiple. Usually asymptomatic, or could have: cough, incidental chest infection, exacerbation of asthma/COPD. Diagnosed by: lung nodules on imaging + Aspergillus (either by biopsy or positive IgG in blood)
Chronic Cavitary Pulmonary aspergillosis: immunocompetent hosts, have formation and expansion of pulmonary cavities over months. Diagnosis: 1+ cavity on chest imaging +/- aspergilloma, at least one of these symptoms (fever, weight loss, fatigue, cough, sputum, hemoptysis, SOB), and positive aspergillus IgG.
Chronic fibrosing pulmonary aspergillosis: late-stage of chronic cavitary pulmonary aspergillosis, with progression to extensive fibrosis. Diagnosis- same as above, but with fibrosis (on biopsy or CT) and major impairment in lung function.
Subacute invasive pulmonary aspergillosis (aka chronic necrotizing pulmonary aspergillosis): patients with some degree of immuncompromise - they present with progressive features over 1-3 months. Hyphal invasion of tissue, cavitating pneumonia/consolidation, may have detectable Aspergillus antigen (galactomannan) or Aspergillus IgG in the blood. Confirmation requires biopsy of pulmonary lesion.

Question 30

Diagnostic criteria for ABPA

Answer 30

As per UpToDate and review course slides (ISHAM criteria):
Predisposing condition (1 must be present): Asthma or CF
Obligatory criteria (both must be present)
Aspergillus positive SPT or sIgE
Elevated serum IgE, typically >1000 IU/mL, but lower may be acceptable if meets all other criteria
3) Other criteria (at least 2 must be present)
Precipitating serum antibodies to A. fumigatus or elevated serum Aspergillus IgG by immunoassay
Radiographic pulmonary opacities consistent with ABPA
Eosinophils >500cells/uL in steroid-naive patients

Question 31

treatment of ABPA
with CF

Differential diagnosis:
ABPA
CF with sensitization to aspergillus
Allergic fungal rhinosinusitis to aspergillus
Regular allergic rhinitis with aspergillus sensitization
Another type of aspergillus-related lung disease: eg. subacute invasive pulmonary aspergillosis
Hypersensitivity pneumonitis (aspergillus is the antigen for malt worker’s lung- source: malt, tobacco, soy)

Answer 31

Treatment:
Long-term corticosteroids → prednisone (0.5-1mg/kg) for at least 14 days; taper and continue for 3-6 months
Monitor response with monthly total serum IgE
Steroid therapy can be combined with antifungal therapy (itraconazole or voriconazole for at least 16 weeks)
Recommendations vary: some say antifungals should be combined with steroids as primary therapy, others say to reserve them for cases that fail to respond to initial course of steroids or exacerbations

Prednisone 0.5-1mg/kg daily x 14 days, taper and continue for 3-6 months with monthly monitoring of total serum IgE
+/- antifungal therapy (either itraconazole or voriconazole)
Regular CF care: optimum nutrition (high fat diet, ADEK vitamin supplements, pancreatic enzymes), chest physiotherapy, mucolytics (hypertonic saline, DNAase), bronchodilators, antibiotics if any coexistent bacterial infection
Avoid exposure to places with high mold spore counts - eg. damp basements, barn, compost heaps

Question 32

name 5 hev b proteins and their associated allergy

Answer 32

hev b 1, 3 spina bifida

hev 5 avidic protein - kiwi
hev 6 - hevein protein - BAC
hev 7 - patatin - potato
hev 8 - profilin - celery

hev 11 - chitinase - BA
hev 12- LTP - peach

Question 33

A previously healthy 35 year old woman has worked as a secretary in the busy intensive care unit of a hospital. She sits at a desk in the patient care area but has no direct contact with the patients. During the past three months she has suffered from wheezing, cough, and sneezing only while at work. In the last 2 weeks the wheezing has persisted over the weekends. What do you suspect is causing her disease? How would you prove it? Briefly explain how the problem might be managed.

Answer 33

ddx

Differential diagnosis:
Occupational asthma = airway hyperresponsiveness, inflammation and obstruction due to particular workplace exposure (de novo asthma diagnosis, or recurrence of quiescent asthma)
Work-exacerbated asthma = occurs in patients with preexisting active asthma, with increased bronchospasm related to work exposure
Hypersensitivity pneumonitis (doesn’t really fit the pattern of symptoms though! *HP does not typically have wheeze!!)
Latex allergy

Possible agents:
Latex
Formaldehyde
Antibiotics (especially beta lactams) - eg. are meds being compounded near her work desk
Psyllium (used in laxatives)
Anyone painting nearby- Paints can contain phthalic anhydride, trimellitic anhydride
Cleaning agents used nearby → chlorhexidine, glutaraldehyde,

Question 34

OA investigations

Answer 34

Detailed exposure history - current occupation, past occupations, exposures/timing/pattern of symptoms (eg. any changes in work processes preceding symptoms, any unusual exposure in 24h pre-initial asthma symptoms, do symptoms differ when away- weekends/holidays, worse at work?), protective devices used, MSDS sheets, history of atopy
Confirm asthma with spirometry, including pre/post bronchodilator, or methacholine challenge
Choose method to confirm that her asthma is due to specific occupational sensitizing agent:
Serial spirometry or serial PEF → should be measured outside the workplace and serially every 2 hours at work and at home for 2 weeks
If PEF lower at work, with variability >20% = consistent with OA
FEV1 reduction by 15-20% after exposure suggestive of OA
Methacholine challenge: performed when patient is symptomatic and at work (negative test excludes OA); can also compare methacholine challenge when patient away from work for 2 weeks and then again after workplace exposure (a drop in PC20 by 2 doublings is considered significant)
Skin prick test / SIgE testing to some HMW allergens may be helpful → in this case, could test for latex, psyllium
When diagnosis remains unclear → referral for inhalational challenge (= gold standard)

Question 35

mechanism of OA

Answer 35

Brief summary of above:
HMW antigens = cause IgE-mediated, ag, DC, Th2, IL45 Eo unflmamation and IgE calss swtich by B cell
LMW antigens = either IgE (by acting as haptens) or non-IgE
RADS = non-immunologic, neurogenic inflammation
- irtitant release Susbtance P, neurkonin and ROS - No inflm

Can be IgE-mediated, when the culprit agent is a high molecular weight antigen (eg. animal proteins, flour, latex, enzymes)
These antigens lead to sIgE production → Th2 response
Or, some low molecular weight antigens (eg. reactive chemicals) act as haptens and therefore result in IgE-mediated mechanism (eg. Phthalic anhydride, trimellitic anhydride, platinum salts, nickel, epoxy, penicillin)
Non-IgE mediated mechanism → low molecular weight antigens, mechanism is unclear but NOT IgE-mediated. Examples: plicatic acid, isocyanates
Nonimmunologic mechanism:
Eg. Reactive airway dysfunction syndrome is a subset of OA that occurs after a single, high-level exposure (often LMW antigens). Examples- chlorine gas, hydrochloric acid, ammonia, hydrogen sulfide
Mech not fully known, but there is extensive denudation of epithelium, resulting in airway inflammation and exposure of nerves leading to neurogenic inflammation (with release of substance P) and nonspecific activation of mast cells
Epithelial damage also leads to airway remodeling

Question 36

occupational exposure in furniture factory under the following headings. DDX, Pathogenesis. Diagn`osis. Mx. Pathogenesis, diagnosis and management as for the previous cases

Answer 36

Occupational asthma
Work-exacerbated asthma
Hypersensitivity pneumonitis
COPD
Vocal cord dysfunction 

Irritant:
Plicatic acid (from western red cedar), trimellitic anhydride (plastics/paint), abietic acid (glues), metals (platinum salts, potassium dichromate)
Pathophysiology:
All the possible irritants are low molecular weight antigens; thus could either act as haptens and cause IgE-mediated reaction → Th2 response, or could be non-IgE mediated

Question 37

List 5 mechanisms where cytokines contribute to clinical asthma

Answer 37

Th-2 lymphocytes produce the following cytokines:
IL-3 → survival factor for eosinophils and basophils
IL-4 → helps in differentiation of uncommitted T cells into Th2 cells, switching of IGs synthesis to IgE production, and mediates eosinophil/basophil/T cell recruitment
IL-5 → regulates eosinophil production and survival
IL-13 → contributes to airway eosinophilia, mucous gland hyperplasia, airway fibrosis and remodeling
GM-CSF → survival factor for eosinophils
IL-9 → promotes hypertrophy/hyperplasia of submucosal glands, leading to excess mucous production
TNF alpha (produced by mast cells) → recruits and activates inflammatory cells, and alters the growth of airway smooth muscle cells

Question 38

immunological asthma cause

Answer 38

Due to genetic/environmental influences, there is an overexpression of Th2 response relative to Th1
Thus, initial allergen exposure → Th2 response → production of specific IgE which bind to high-affinity receptors on mast cells and basophils → allergen subsequently inhaled and cross links allergen-specific IgE on mast cell surface → rapid degranulation and mediator release (including: histamine, prostaglandin D2, cysteinyl leukotrienes = LTC4, D4, E4) → leads to contraction of airway smooth muscle + stimulate reflex neural pathways
Mast cells also release cytokines/chemokines, leading to the late phase response characterized by influx of inflammatory cells (monocytes, dendritic cells, neutrophils, T cells, eosinophils, basophils) → they release their mediators and cytokines → airway smooth muscle contraction, mucous gland hyperplasia, airway remodeling

Question 39

two mediators that affect asthma

Answer 39

Cysteinyl leukotrienes
LTC4, LTD4, LTE4 - these bind to receptors CysLT1 and CysLT2
When they bind to CysLT1 → these actions are central to the pathogenesis of asthma, as it mediates sustained bronchoconstriction, mucus secretion and edema
Hence montelukast and zafirlukast (LTRA) act as antagonists by preventing binding to the cysLT1 receptor
PGD2
Binds to PGD2 receptor on mast cells, basophils and eosinophils → mediates migration of Th2 lymphocytes, delays Th2 cell apoptosis, and stimulates Th2 cells to produce IL-4, IL-5 and IL-13
Has bronchoconstrictive effects
Has chemokinetic effects → it’s a potent eosinophil chemoattractant

Question 40

what are tachykinins and what is their role in asthma

Answer 40

Tachykinins are potent bronchoconstrictors (NK2 receptors are present on smooth muscle in both small and large airways)
Substance P can cause mast cell degranulation
Tachykinins cause chemotaxis of neutrophils into the airways
Substance P modulates the chemotaxis, proliferation and activation of lymphocytes
Tachykinins can activate mesenchymal cells in the airway, which may play a role in airway remodeling

Question 41

evidence of asthma contribution to inflammation

Answer 41

Evidence of contribution of inflammation:
Airway biopsies obtained by bronchoscopy
have demonstrated that inflammation in asthma generally involves the same cells that play prominent roles in the allergic response in the nasal passages and skin, whether the individual is atopic or not
Response to medications:
Treatment with Omalizumab, antihistamines and LTRAs block significant portions of both early and late phase responses to allergens
Specifically LTRAs → evidence for the role of mast cells, basophils and leukotrienes
Treatments that target asthma inflammation (eg. glucocorticoids, anti-IgE) block the late phase response and improve control of asthma
Biologics targeting IL-4, IL-5, IL-13 → further confirmation of the role of Th2 cytokines in asthma

Question 42

role of following in asthma

1) tiotropium
2) macrolide

Answer 42

This is a long acting muscarinic antagonist (LAMA)
Mechanism of LAMA: prevent acetylcholine-mediated bronchoconstriction by competitively antagonizing M3-receptors in the airways, and thereby permitting bronchodilation
Long duration of action → 9 hours
Generally safe and well tolerated; Side effects: dry mouth, mydriasis, urinary retention, metallic taste
Tiotropium bromide soft mist inhalation therapy is safe and effective in improving lung function and reducing severe asthma exacerbations in adults and adolescents with uncontrolled asthma despite ICS + LABA
Dose: 5mcg once daily (2 inhalations of 2.5mcg) by soft mist inhaler may be considered as add on therapy for individuals 12yrs+ with severe asthma who remain uncontrolled despite combo ICS/LABA therapy.

Macrolides have anti-microbial and anti-inflammatory effects – in individuals with asthma, they have been shown to decrease neutrophil numbers and IL-8
In adults (18 yrs+) with severe asthma, there is limited evidence that the chronic use of macrolides may decrease the frequency of exacerbations.
Inflammatory phenotype does not consistently predict response to macrolide treatment. 
Macrolides are generally well tolerated. However, should be avoided in individuals with a prolonged QTc interval. 
Increased incidence of bacterial resistance and impaired hearing tests have been observed in long-term treatment with macrolides. 
Data for pediatric and adolescents are inconclusive

Question 43

role of nfidipine and immunotherapy in asthma

Answer 43

practice guidelines, due to potential for serious anaphylactic reactions
Cochrane review confirmed its efficacy in reducing asthma symptoms and the use of asthma medications, and improving airway hyperresponsiveness
Evidence also suggests that immunotherapy may prevent the onset of asthma in atopic individuals
Should be considered on a case-by-case basis; may be add-on therapy in patients using ICS monotherapy, combination ICS/LABA, ICS/LTRAs and/or omalizumab if asthma symptoms are controlled
Should NOT be initiated in patients with uncontrolled asthma or FEV1 <70%
Source: AACI Asthma Review
Nifedipine
Good option for treating hypertension in asthmatics - as per UTD, a low dose thiazide alone OR with a calcium channel blocker = preferred regimen
CCBs have theoretical advantages of opposing muscle contraction in tracheobronchial smooth muscle, inhibiting mast cell degranulation, and possibly reinforcing the bronchodilator effects of beta agonists
Nifedipine can antagonize the bronchoconstricting effects of antigen, histamine, or cold air
In clinical trials → they either modestly improve or do not affect pulmonary function in asthmatics
See below for more about antihypertensives in asthma/COPD (… for us pediatricians!)
Source: UTD Treatment of hypertension in asthma and COPD

Question 44

what contirbtues to systemic absorption more

swalloed or inhaled ICS

Answer 44

ICS 10-40% is inhaled other is swallowed) and whats INHALED is absorbed direct into systemic vs whats sawlloed goes into first pass

Question 45

whats the target of montelukast

Answer 45

cys LT1

which binds to LTC4/d4/e4

used for:
Exercise-induced bronchospasm
Allergic asthma and allergic rhinitis, especially with polyposis
AERD

What targeting using these agents essentially does:
Anti-inflammatory effects including
Reduced eos circulating and in sputum
Reduced exhaled nitric oxide
Reduced nonspecific bronchial hyperresponsiveness
Bronchodilatory action (as described above is a major role given potent bronchoconstrictive capacity of CysLTs