Page 79 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
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­basal membrane. ASM hyperplasia (me- of disease and are ideal tools for studying indi- 79
diated through growth factors, epithelial in- viduals who have or are suspected to have ex-
flammatory mediators, and extracellular ma- ercise-induced bronchoconstriction3. lung function tests to be used in severe asthma: spirometry and bronchodilator test ...
trix components) is a key mechanism, most
probably irreversible with treatments availa- The response to bronchoprovocation
ble nowadays5. agent is dose (or concentration) dependent.
Since it is clinically not feasible to test both
Epithelial Damage and Inflammation hyperreactivity and hypersensitivity (due to
possibility to induce severe obstruction in for-
Epithelial damage (e.g., in viral bronchi- mer), arbitrary point of decease of FEV1 is
tis)10 can be a reason for dysfunction in air- chosen as 20% of drop of FEV1 comparing
way smooth muscle innervation (particularly the FEV1 after inhalation of normal saline
parasympathetic and NANC-non-cholinergic (0.9% NaCl). Patterns of response are shown
non-adrenergic) and consequently causing a on Figure 1.
transient BHR9,11. In COPD and smokers’ air-
ways that mechanisms are even more prom- Airway obstruction is a term that is de-
inent. Repair process could lead to collagen rived from spirometric flow-volume curve
deposition, basal membrane thickening and and is defined as a decrease of Index Tiffene-
permanent airway narrowing12. au (FEV1/VC ratio) for 12% below lower
limit of normal. Decrease of expiratory flows
Techniques to Measure Bronchial per-se (FEV1 or PEF) is not sufficient for con-
Hyper Responsiveness firmation of obstructive ventilatory defect but
can be used (after we define obstruction) as a
Direct and Indirect Bronchial Challenge marker of degree of obstruction (mild, mod-
Tests erate, severe). Since in many cases asthma
(as predominantly large/medium airway dis-
‘Direct’ BPTs measure airway smooth mus- ease) can affect small airways too, impulse
cle function, whereas the ‘indirect’ tests re- oscillometry and/or body plethysmography
flect airway inflammation. Airway caliber measurement are used to define the degree of
is important in determining response to di- bronchial system involvement.
rect stimuli2. Therefore, the direct challenges
function best to exclude current asthma when Variability of airway obstruction usually
they are negative. By contrast, all the indirect (but not always i.e., in non-eosinophilic asth-
challenges (exercise, eucapnic voluntary hy- ma) parallels the intensity of airway asthmat-
perpnoea, hypertonic saline, adenosine mono ic inflammation. The variability should be as-
phosphate (AMP) and mannitol) critically de- sessed over time; the best tool is to use PEF
pend on the presence of airway inflammato- measurements for at least 2 weeks, three times
ry cells4. Many of the indirect challenges are daily at home environment in the period,
dose limited meaning that it is not possible when the patient describes asthmatic symp-
to push the dose beyond a certain limit that toms. Diary of those measurements (best pro-
is limited by physiology (exercise, eucapnic vided by electronic PEF meter, since compli-
voluntary hyperpnoea) or solubility (AMP). ance of a patient with ordinary PEF meter is
Comparative studies have demonstrated that less than 30%) is assessed day by day and ex-
the indirect challenges are highly specific but cess variability is determined by more than
have a relatively low sensitivity compared 20% fluctuation of PEF.
with methacholine7. Due to their high speci-
ficity (and low sensitivity), indirect challenge Reversibility of obstruction is assessed by
tests function best to confirm the presence bronchodilator test. Improvement of airway
obstruction after short-acting bronchodilator
(in Slovenia standard is 400mcg of salbuta-
mol) for at least 200ml increase on either FVC
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