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Chapter 3B
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Diagnosis of Allergies and Asthma
Sundeep Salvi,
1,2,
* Deesha Ghorpade1 and Monica Barne
1
ROLE OF SPIROMETRY IN THE DIAGNOSIS AND
MANAGEMENT OF ASTHMA
Introduction
Spirometry is the “gold standard” objective diagnostic test for obstructive airways diseases,
including asthma. The hallmark feature of asthma is expiratory airflow limitation and its variability
with time, either with or without treatment. Spirometry helps in documenting both of these features.
The spirometer was invented by Sir John Hutchison from the UK who used a water seal drum
connected to a calibrated scale. This spirometer measured the volume of air exhaled by the patient
after taking a full inhalation. Hutchison called this volume as vital capacity (VC) because he was
able to show through research that this volume of air was vital for survival and strongly predicted
life span. When this volume of air was removed slowly, it was called slow vital capacity (SVC) and
when removed with force, it was called forced vital capacity (FVC). For almost a century, this was
the only parameter that was measured using spirometry. In 1945, Robert Tiffeneau from France gave
a time component to the VC, measuring the volume of air exhaled in unit time. The volume of air
exhaled in the first one second was called FEV1 or forced expiratory volume in the first 1 second.
Subsequently, the volume of air removed in 2 seconds was called FEV2 and so on.
In the presence of airflow obstruction, the volume of air removed in the first 1 second (FEV1)
is lower and therefore the ratio between FEV1 and FVC reduces. A ratio of FEV1/FVC < 0.75 in
adults and < 0.85 in children (up to 18 years) indicates airflow obstruction that could be suggestive
of asthma.
There are two flow rates that are measured by the flow sensor-based spirometers, PEFR and
FEF
FEF
value indicates obstruction in the total respiratory tract, while the FEF
smaller airways.
the two volumes (FEV1/FVC) and the two flows (PEFR and FEF
used volume displacement methods to measure lung volumes. They were more accurate for
measuring FEV1 and FVC. But they could not give the two flow rate values easily, were huge and
. The PEFR is the highest flow rate achieved during a forced exhalation maneuver and
25%–75%
is the average flow rate between 25% of the FVC to 75% of the FVC. The PEFR
25%–75%
The five key parameters in spirometry are the two volumes (FEV1 and FVC), the ratio between
25%–75%
represents flow in the
25%–75%
). The earlier spirometers
1
Pulmocare Research and Education (PURE) Foundation, Pune, INDIA.
2
Symbiosis International (Deemed University), Pune, INDIA.
* Corresponding author: sundeepsalvi@gmail.com
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Figure 1. Normal spirometry graphs.
bulky, were not portable and were even difficult to maintain. They were therefore replaced by flow
sensor-based spirometers, which were small and portable, gave both the volume time and flow
volume curves, were easy to maintain and were cheaper. Various flow sensors are used to measure
flow, including pneumotachographs, turbines, anemometers and ultrasonic flow sensors. Flow is
converted into volume by multiplying it with time.
The two basic graphs that we get in spirometry are the volume time Graph and the Flow Volume
Loop (Figure 1).
In the volume time graph (Y-axis is volume, X-axis is time), we see a sharp increase in the
volume in the first one second, which reaches the highest point at around 2–3 seconds and then
settles down as a plateau. The plateau is a flat line which indicates that all the air has come out from
the lungs and there is no more left to come out. In healthy individuals, this plateau is reached within
the first 2 to 3 seconds. The highest point on the Y-axis is called the FVC. The volume of air exhaled
in the first 1 second is the FEV1. The volume time graph also gives the Forced Expiratory Time
(FET), which indicates when the flow stopped. This is an important quality assurance criterion.
In the flow volume loop, the flow is plotted on the Y-axis and the volume on the X-axis. When
the patient starts exhaling, the flow rate suddenly increases to reach a peak, after which it shows a
slow and smooth decline until it reaches the X-axis to give the FVC value. The highest flow rate
achieved is called the Peak Expiratory Flow Rate (PEFR), which is also obtained from a peak flow
meter (PFM). The flow rate when 50% of volume was exhaled is called the Forced Expiratory Flow
at 50% (FEF
values from FEF
). Similarly, values for FEF
50%
25%–75%
is called as FEF
and FEF
25%
. After the compete exhalation, the subject is asked
25%–75%
are also obtained. The average of flow
75%
to again inhale in forcefully. The expiratory maneuver looks like the shape of a triangle and the
inspiratory flow rate looks like the shape of a semicircle.
The maneuver of spirometry can be divided into six steps as below:
1. Exhale out completely
2. Take a deep inhalation and fill up the lungs completely
3. Hold the mouthpiece in between the teeth, clasp it in an airtight manner and seal the lips
4. Blow out air into the mouthpiece with maximum force
5. Continue to blow out the air till a plateau of 1 second is obtained or up to a maximum of
15 seconds
6. Inhale deeply and forcefully
Spirometry Procedure
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Since this is an effort-dependent test, the instructions that are given to the patients have to
be very clear to ensure that the patient understands how to perform each step. A demonstration
to the patient will be useful and necessary. The skill of the technician in using voice modulation,
effective body language and demonstration is of utmost importance. A few trials runs with only the
mouthpiece also help the patient to perform the test correctly. We need to get three acceptable graphs
from the patients and of the three, the two best need to be reproducible.
The Criteria for Acceptability Are as Below (Graham et al. 2019)
1. Maximal inspiration before exhalation
2. Goodstart.Nodelay/hesitationinthestart,theBEV(backextrapolatedvolume)mustbe≤5%
of FVC or 0.100 L whichever is greater; best seen in volume/time graph
3. No evidence of faulty zero-flow setting/no evidence of a leak
4. Maximal effort right from the beginning of the expiratory blast
5. Smooth and continuous exhalation, no cough in the first second of expiration, no glottic closure,
and no early termination
6. Must achieve one of these three EOFE (End of Forced Expiration) indicators.
i. Expiratoryplateau(≤0.025Linthelast1secofexpiration)
ii. ExpiratoryTime≥15sec
iii. FVC is within the repeatability criteria or is greater than the largest prior observed FVC
The acceptability criteria can be analyzed by looking at the shape of the curves and is beyond
the scope of this chapter.
Criteria for Reproducibility
The spirometry test is said to be reproducible or repeatable when the difference between the highest
two FVC values and the highest two FEV1 values is less than 150 mL.
Interpretation of Spirometry for Diagnosis of Asthma
Interpretation begins right from when the participant is performing the spirometry test. If a patient
is able to blow out effortlessly for more than 10, 12 or 15 seconds it indicates severe airflow
obstruction. Just by looking at the shape of the spirometry graphs, we can deduce the presence of
airflow obstruction and also determine its severity. Every graph or rather every spirometry report
comes with the pre-plotted predicted values which are derived from the patient’s demographics
and indicates where the patient’s values should ideally be. The Global Lung Initiative (GLI) is now
recommended as the predicted equation to use.
By comparing the patient’s FEV
, FVC, PEFR and FEF
1
values we can diagnose the presence of airflow obstruction. The shape of the curves as mentioned in
Figure 2 below depicts the interpretation.
Interpreting the spirometry report by looking at the values given in the algorithm (Figure 3).
Before you interpret the report by looking at the shape of the curves, ensure that the X:Y scales
are appropriate (For flow volume: X-axis 0.5 Lt to Y-axis 1 Lt; For flow time: X-axis 1 sec to
Y-axis 2 Lt). The first value that we look at is the FEV1/FVC ratio. It is said to be normal if it is
more than 0.7. Next, if the FVC percentage predicted is also > 80% then the spirometry report is
considered to be normal. But if the FVC percentage predicted is reduced then it indicates presence of
restrictive lung disease (RLD), which will then need to be confirmed by body box plethysmography.
A new term coined for this is Preserved Ratio Impaired Spirometry (PRISM). 30% show evidence
of frank RLD on the body box, 20% revert back to normal and around 50% end up developing
frank obstructive airways disease. If the FEV1/FVC ratio is reduced below 0.7, then it indicates
values with the predicted
25%–75%
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Figure 2. Interpretation by looking at the spirometry graphs.
Figure 3. Spirometry interpretation algorithm.
obstructive airway disease (OAD). In this case if the FVC percentage predicted is more than 80%,
then it is mild or moderate airflow obstruction. If the FVC percentage predicted is also reduced
below 80%, then it indicates either a mixed obstructive plus RLD or a severe airflow obstruction,
where the FVC has reduced due to air trapping.
Role of Spirometry in Assessment of Asthma (GINA 2021)
The Global Initiative for Asthma 2021 (GINA 2021) recommends documentation of variable airflow
obstruction at the time of diagnosis and before initiation of controller therapy.
To confirm variable expiratory airflow limitation:
• Perform spirometry
• If FEV1 is reduced and FEV1/FVC is < 0.75 in adults and < 0.85 in children, it indicates airflow
limitation (for COPD a cut-off value of 0.70 is recommended)
To demonstrate bronchodilator response (BDR) variability on spirometry:
A) Reversibility to Bronchodilator
• Record baseline spirometry
• Administer 200 to 400 micrograms of Albuterol (Salbutamol)
• Wait for 15–20 minutes
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• Repeat the spirometry
• If the FEV1 improves by > 12% and > 200 Ml, then it suggests the possibility of asthma. If the
FEV1 increase is to the tune of > 15% and > 400 ml, then it is most certainly asthma. The cut-off
for good BDR for children is 12% only.
Note: Before performing bronchodilator reversibility, and if the patient is on a regular inhaled
short-acting beta agonist (SABA) or a long-acting beta agonist (LABA), then the following drugs
have to be withdrawn before performing the spirometry. Table 1 depicts the optimum bronchodilator
withholding time prior to testing.
B) Reversibility to Inhaled Corticosteroid
• Record Baseline spirometry
• Initiate controller therapy with Inhaled Corticosteroids
• Repeat spirometry after 4 weeks of ICS
• If the FEV1 improves by 12% and 200 ml after 4 weeks of ICS, then it is likely to be asthma
• For oral corticosteroids, follow-up spirometry is to be done 2 weeks later.
C) Positive Exercise Challenge Testing
Fall in FEV1 by 10% and 200 ml after an exercise challenge in adults and fall in FEV1 of > 12% in
children indicate positive exercise testing and confirm variable airflow obstruction
D) Positive Bronchial Challenge Testing
Fall in FEV1 by > 20% from the baseline value on challenging the airways with a
broncho-provocative agent like methacholine, histamine or mannitol indicates the variable nature of
the asthmatic airways. Histamine and methacholine cause direct bronchoconstriction, while adenosine
monophosphate activates the inflammatory cells to release histamine and other broncho-constricting
substances which simulate the underlying inflammation that happens in asthma.
E) Excessive Variation of Lung Function Between Visits
If in-between visits, the FEV1 varies between > 12% and > 200 ml, it indicates the likely
presence of asthma. In adults, an FEV1/FVC < 0.7 indicates the presence of obstructive airway
disease, which could be either asthma or COPD. After giving a short-acting bronchodilator, if the
FEV1/FVC becomes > 0.7, then it indicates a diagnosis of asthma, while if the post-bronchodilator
FEV1/FVC remains < 0.70, it indicates a diagnosis of COPD or asthma with fixed airflow obstruction.
As mentioned earlier, for asthma a cut-off of 0.75 is used instead of 0.70.
Instead of the fixed ratio for FEV1/FVC, the lower limits of normal can also be used, but this
is beyond the scope of this chapter. Similarly, FEV1 and FVC values instead of expressing them as
% predicted are now being recommended to be expressed as a z-score (lower 5th percentile value).
Table 1. Bronchodilator medication withholding time.
Bronchodilator Medication Withholding Time
Short Acting Beta Agonists (SABA) (e.g., albuterol or salbutamol) 4–6 hrs
Short-acting muscarinic antagonist (SAMA) (e.g., ipratropium bromide) 12 hrs
Long-acting Beta Agonists (LABA) (e.g., formoterol or salmeterol) 24 hrs
Ultra-LABA (e.g., indacaterol, vilanterol or olodaterol) 36 hrs
Long-acting muscarinic antagonist (LAMA) (e.g., tiotropium, umeclidinium, aclidinium or
glycopyrronium)
36–48 hrs
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Spirometry in Children
It is a challenge to do spirometry in children, but trained and experienced technicians with patience,
can get children as young as three years to perform spirometry. It is important to have a setup that is
child-friendly and equipment that has incentives for the child to perform the test with the best effort.
Children may exhale almost all air within the first 1 sec, hence the FEV
FEV1 for interpretation. The criteria for repeatability are also lower for children < 6 years of age.
may be used instead of
0.75
ROLE OF PEAK FLOW METER IN THE DIAGNOSIS AND
MANAGEMENT OF ASTHMA
Introduction
Although spirometry is the gold standard diagnostic test for obstructive airways diseases, there are
several challenges to using spirometry in clinical practice, i.e., difficulty in getting the test performed,
lack of availability of spirometers and difficulty in interpreting the report. These challenges can be
overcome by using a simple, easy to perform and easily available tool called the peak flow meter
(PFM) (Figure 4). The PFM measures the maximum or peak flow rate that the patient can achieve
during maximal exhalation. It measures the airway patency of all the divisions of the airways but is
more biased toward the larger airways. The peak flow is achieved at around 200 milliseconds, the
test therefore does not need to be performed for more than a second (Dobra 2018).
The PFM is a cylindrical tube of around 10 inches (although there are different sizes and shapes
available) that has a slot in the middle for the scale with markings usually from 0 to 800 L/min. One
end is for the mouthpiece and the other end is for the air to exit. The marker moves ahead when one
blows through the mouthpiece and stops at the maximum flow rate achieved. There are electronic
PFMs too that have started becoming available.
Figure 4. The PFM. The EU represents the European union scale of the markings.
Procedure for Recording the PEFR Value
• Coach the patient
• Fix new mouthpiece to PFM
• Place the indicator at “0” (zero). Hold the PFM in such a way that the fingers are not covering
the slot and the indicator can move freely in the slot
• Take a deep breath and fill the lungs with as much air as possible
• Place the PFM in your mouth and seal your lips. Make sure that the tongue is not inserted in the
mouthpiece
• Blow out as HARD and as FAST as you can for not more than 1 sec
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• Note down the number you get from the scale
• Repeat the above steps two more times
• Record the “highest” of the three values obtained
What Is the Normal PEFR?
Just like spirometry, there are predicted equations for PEFR based on age, height, gender and race.
From the equations, we can derive the normal predicted value for an individual. The patient’s value
is to be compared with this value and a value within 80% of the predicted value is considered to
be normal. The predicted equation used is usually the Nunn and Greg equation with or without a
correction factor as per the race. There are indigenous predicted equations developed by different
countries, which are advisable to be used for the local population, including India (Kodgule R.R.
J. Postgrad. Med. 2014).
The PFM has several roles in clinical practice (Dobra 2018):
1. For diagnosis of asthma
2. For daily monitoring of asthma and assisting in asthma self-management plan
3. For evaluating response to treatment
4. For identification of asthma triggers
5. For diagnosis of occupational asthma
6. Severity assessment of acute flare-up of asthma
PFM is comparatively less reliable as compared to spirometry in the diagnosis of asthma in
children but may be used in combination with the clinical presentation. For day-to-day monitoring
of asthma in children, peak flow readings and Asthma Control Tests are independent of each other
and are well correlated (Buzoianu et al. 2014; Chan et al. 2009).
The Global Initiative for Asthma (GINA) 2021 report recommends the use of the peak flow
meter to diagnose asthma in three different ways (GINA 2021):
1. Reversibility to four weeks of inhaled corticosteroids (ICS): In patients with a history suggestive
of asthma, record the baseline PEFR reading. Initiate ICS treatment with/without a long-acting
bronchodilator and continue for four weeks and then repeat PEFR value. Improvement in PEFR
by more than 20% after four weeks of ICS treatment indicates a strong likelihood of asthma.
2. Diurnal variability: Like many physiological parameters the PEFR also shows diurnal variability
with the PEFR values being lower in the mornings and higher in the evenings. However, in
healthy subjects, this diurnal variability is not more than 10%. To record diurnal variability, the
patient is given a PFM and is asked to record the values in the morning and the evening for two
weeks. The daily diurnal variability is calculated by the following formula:
PEF variability = (Highest PEFR – Lowest PEFR)/Mean of highest and lowest PEFR.
In adults, if the PEFR variability is > 10% and in children > 13%, it indicates significant diurnal
variability, consistent with the diagnosis of asthma.
3. Negative reversibility to exercise challenge: If the PEFR value decreases by 15% after an
exercise challenge then it indicates the presence of variable airway obstruction, suggestive of
asthma.
Day-to-Day Monitoring of Asthma and Prevention of an Acute Exacerbation
The PFM is probably a better tool for the day-to-day monitoring of asthma at home, particularly for
patients who are poor perceivers of their symptoms, and consequently is extremely useful for the
prevention of an acute exacerbation (Table 2).
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Table 2. Zones of asthma control basis the patient’s personal best value (Adeniyi and Erhabor 2011).
Green Zone: The patient’s peak low reading is between 80–100% of the patient’s personal best. This is a zone where the
patient’s asthma is well controlled, without any symptoms, dietary or activity limitation, no night-time awakenings and
no need for reliever medication.
Yellow Zone: In the Yellow zone, the patient’s PEFR is reduced to below 80% of the personal best and lies between
50% to 79% of the personal best value. This is an “alert” zone indicating that the asthma is not under control and the
patients may develop an acute exacerbation at any time.
Red Zone: When the PEFR reading reduces to below 50% of the patient’s personal best, it indicates that the patient is
likely having an acute asthma exacerbation and should be managed aggressively.
Concept of Personal Best
A patient with asthma may never achieve his or her predicted value. Hence it is important to
identify the individual’s own personal best value, which can then be used as the baseline value for
comparison of the current PEFR value over time. The personal best value is the highest PEFR value
that the patient can attain when his or her asthma is well-controlled on medications and is free of
symptoms. This is usually after three weeks of inhaled corticosteroid therapy (Reddel et al. 2004).
This value is noted as the baseline value and any decrease by more than 20% of the personal best
PEFR should be taken seriously.
A reduction below 80% from the personal best indicates the onset of an impending exacerbation.
When detected beforehand, the exacerbation can very well be prevented by either stepping up
therapy in the form of a short course of oral steroids or stepping up the dose of ICS.
Monitoring of Asthma Control During Step Down of Treatment
Response to the treatment of asthma can be objectively evaluated by monitoring the improvement
in PEFR. The PEFR is also a good tool for daily home monitoring of asthma control and deciding
when the medication can be tapered or stopped. This gives the patient and the caregiver a sense
of security when the dose is being tapered down and reassuring that after tapering/stopping the
medicines the patient is indeed tolerating the regimen.
Trigger Identification
When monitoring the PEFR regularly at home, the observation of a sudden drop in PEFR on a
particular day, suggests that it may indicate exposure to a potential trigger on that day.
Diagnosis of Occupational Asthma
The PEFR is the diagnostic tool for occupational asthma as it can be carried to the place of work and
the PEFR recording can be obtained as frequently as every 1–2 hours. Ideally, the PEFR value should
be taken after waking up and thereafter every 2 hours till the subject returns home. A record of these
is kept for at least four weeks. If the tracing shows a reduction in the PEFR values during working
days and an improvement on holidays, then this is a strong indicator of occupational asthma.
The PFM is therefore a very useful and handy tool for the diagnosis of asthma, monitoring
response to treatment, identifying asthma triggers and diagnosing occupational asthma. More
importantly, home-based monitoring with a PFM can help detect an asthma exacerbation several
days in advance, especially among the poor perceiver group of asthma symptoms.
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ROLE OF FRACTIONAL EXHALED
NITRIC OXIDE (FeNO) IN ASTHMA
Introduction
The fractional exhaled nitric oxide or FeNO is a simple, non-invasive, quantitative, reproducible,
safe, and easy-to-perform test that helps in detecting type-2 driven eosinophilic airway inflammation
that is characteristic of allergic asthma. Several international guidelines recommend this as a useful
additional parameter supporting treatment decisions in patients with suspected asthma (Dweik
et al. 2011). High FeNO levels in subjects with asthma predict the likelihood of a good therapeutic
response to ICS. FeNO can also be used to evaluate compliance and adherence to ICS.
Nitric Oxide and Its Importance in Asthma
Nitric oxide (NO) is a gas produced by different cells in the lung that play an important role in lung
biology. Airway epithelial cells are the predominant source, and three different isoforms of the enzyme
nitric oxide synthase are responsible for its production. Eosinophils are also an important source of
NO, especially in severe asthma. It functions as a vasodilator, bronchodilator, neurotransmitter and
inflammatory mediator. FeNO acts locally as an autocoid, paracrine mediator or neurotransmitter. It
has bactericidal and viricidal properties and a cytotoxic effect on tumor cells. NO is a highly reactive
molecule and has both direct as well as indirect oxidant properties. Under physiological conditions,
NO acts as a weak bronchodilator and anti-inflammatory molecule, while at higher levels it acts as
a pro-inflammatory mediator in the lung and increases bronchial hyperresponsiveness. Levels of
FeNO correlate with the number of eosinophils in the induced sputum or bronchoalveolar lavage
and correlate with bronchial inflammation.
Measurement of FeNO
FeNO can be measured using several commercially available analyzers which differ in methods
of measurement, complexity or setup. Stationary analyzers measure FeNO by chemiluminescent
techniques, while handheld devices measure FeNO using electrochemistry. Ambient NO levels
(produced by motor vehicular exhausts and burning of cooking gas) can be high in polluted cities
and towns and will therefore interfere with the FeNO measurements. Ideally, FeNO measurements
should be performed in a room that has minimal ambient NO levels, but this is quite often not the
case. It is important to at least record ambient NO levels at the time of the test, wherever feasible.
Exhaled NO levels from the lower respiratory tract exhibit significant expiratory flow rate
dependence, suggesting a characteristic diffusion-based process for NO transfer from the airway
wall to the lumen. The higher the flow rate, the higher the FeNO levels, therefore, it is important to
use a constant flow rate of 50 mL/sec during exhalation. Breath-holding should be avoided while
performing the FeNO test as it will give false high levels. Patients should refrain from eating and
drinking for at least 1 hour before the FeNO test. Nitrate-rich foods such as lettuce, spinach and
beetroot increase FeNO levels, while caffeine, alcohol and smoking reduce FeNO levels. Viral
infections of the upper and lower respiratory tract increase FeNO levels, therefore the presence of
these should be recorded while performing the test. If spirometry has to be performed, it should be
performed after the FeNO test, as spirometry has been shown to transiently reduce FeNO levels.
Nose clips are not recommended as this allows the nasal NO to accumulate and promote leakage via
the posterior nasopharynx.
After seating in a comfortable position, the subject should insert the mouthpiece and inhale over
2–3 sec through the mouth to reach total lung capacity, and then exhale immediately without breath
hold at a constant mouth flow rate of 50 mL/sec. This back pressure prevents contamination of NO
from the nose. Usually, a target mouthpiece pressure or flow rate is displayed on the machine screen
or computer screen and the recommended exhalation flow rate should be maintained at around
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50 mL/sec. FeNO levels are expressed in parts per billion (ppb), which is equivalent to nanoliters
per liter.
Clinical Application of FeNO
Earlier studies showed that FeNO levels increased in asthmatics and decreased in response to ICS,
prompting the use of this non-invasive method to diagnose asthma and evaluate its response to
treatment. FeNO, therefore, adds a new dimension to traditional clinical tools, such as history,
clinical examination and spirometry (Lipworth et al. 2020).
FeNO values less than 25 ppb in adults and < 20 ppb in children (5–12 years) are inconsistent
with type-2 allergic asthma. Values greater than 50 ppb in adults and > 35 ppb in children strongly
indicate eosinophilic allergic airway inflammation and a greater likelihood of a good therapeutic
response to ICS. Persistently high values indicate ongoing exposure to high allergen load and/or
non-compliance with the use of ICS. The within-subject variation for FeNO in healthy subjects is
10% or up to 4 ppb. In asthma, the variation is around 20%. A significant response to treatment is
indicated by a 20% decrease if the baseline FeNO was > 50 ppb or a 10% decrease if the baseline
FeNO was < 50 ppb. A meta-analysis concluded that using FeNo to guide ICS dose adjustment
resulted in an overall 42% (24%–55%) reduction in asthma exacerbations (Petsky et al. 2018).
Values that are between 25 to 50 ppb in adults and 20 to 35 ppb in children should be interpreted
in conjunction with clinical and spirometry parameters. FeNO values reduce significantly following
treatment with monoclonal antibodies, such as dupilumab (anti-IL-4/IL-13), especially among
thosewithbaselinevalues≥50ppb,andthiscorrelateswellwithasignificantreductioninasthma
exacerbations.
There is no strong evidence to use FeNO on its own as an objective diagnostic tool for asthma.
Not all asthma is due to eosinophilic airway inflammation. FeNO may help define different
preschool wheezing phenotypes and in assessing the risk of later asthma (Busse et al. 2021). In
atopic schools, children’s presence of respiratory symptoms suggestive of asthma increased FeNO
will add confidence to the underlying diagnosis of asthma (Pijnenburg 2019).
COPD is quite often associated with features suggestive of asthma, such as in the
asthma-COPD overlap. Some studies have suggested that COPD patients with high FeNO levels
respond well to ICS, raising the possibility that FeNO might be used in predicting responsiveness
to inhaled steroids in COPD.
THE METHACHOLINE CHALLENGE TEST TO DETECT
Airway hyperresponsiveness (AHR) is a characteristic feature of bronchial asthma. The airways
narrow excessively in response to both direct and indirect external stimuli when compared to
normal healthy subjects. The methacholine challenge test (MCT) is used to measure and quantify
AHR. It is often used to confirm or exclude a diagnosis of asthma, especially among those with a
history suggestive of asthma but with normal or inconclusive spirometry. Direct stimuli such as
methacholine or histamine are sensitive to diagnose reactive airway disorders, including asthma,
especially if the airway narrowing occurs at a lower dose. Indirect stimuli, such as exercise or
adenosine monophosphate (AMP) induce inflammatory mediator changes, which in turn release
bronchoconstrictor substances such as histamine and other bronchospastic mediators from mast
cells to cause bronchial smooth muscle contraction. Indirect stimuli are more specific for asthma
but are less sensitive. Apart from confirming or ruling out asthma, the MCH test is also useful in
determining high-risk populations such as commercial divers, submarine services, defense recruits
and some occupational exposures.
AIRWAY HYPERRESPONSIVENESS
Introduction
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