Bronchial asthma: diagnosis

Bronchial asthma is not a single disease, but an umbrella term for several clinical and biological phenotypes united by three characteristics: variable respiratory symptoms (wheezing, shortness of breath, chest tightness, cough), episodic limitation of expiratory airflow, and characteristic airway inflammation. Therefore, diagnosis cannot be made by ear or by a single isolated test. It is confirmed by a combination of clinical and objective evidence of variability in lung function over time—this reduces the risk of over- and underdiagnosis and ensures appropriate treatment selection.

Modern diagnostics begin with a precise medical history: when and under what circumstances symptoms appear, what triggers them (allergens, stress, viruses, cold air), how quickly they are relieved, and what triggers them. Next come basic functional tests: spirometry with bronchodilation testing, home peak flow diaries for 2-4 weeks, and, if necessary, exhaled nitric oxide measurement and bronchoprovocation tests. These tools complement, not replace, each other: a negative result from one test does not "rule out" asthma if others indicate its variable nature.

A separate challenge is to detect asthma mimics and associated conditions: vocal fold dysfunction, chronic cough syndrome, gastroesophageal reflux disease, COPD, heart failure, foreign body, and tumors. This is why the algorithm includes "red flags" (hemoptysis, unilateral persistent wheezing, systemic symptoms, late onset), which indicate a more extensive examination and early referral to a specialist. Technique is also important: incorrect maneuvers, failure to adhere to drug withdrawal intervals, and incorrect reference values can easily turn good tests into poor decisions.

Finally, diagnosis must take into account age and context. In children under 5 years of age, objective tests are limited, so they rely on the wheezing phenotype and a treatment trial with reassessment; in adolescents and adults, on a full range of functional and biomarker methods; and in the elderly, on the consistent exclusion of overlapping diseases. The bottom line is simple: airway variability confirmed by diagnosis is the key to personalized treatment, prognosis, and exacerbation risk reduction.

How Diagnosis Is Made in Practice: Logic and "Entry Points"

The diagnosis of asthma is confirmed by two mandatory factors: 1) typical variable respiratory symptoms (wheezing, shortness of breath, chest tightness, cough, varying in time/intensity and provoked by triggers) and 2) objective evidence of variable expiratory flow limitation - "reversibility" or "variability" of lung function parameters over time. This should be documented in the patient's chart, especially before initiating long-term inhaled anti-inflammatory therapy. [1]

If the patient is already receiving inhaled corticosteroids and spirometry is "normal," the diagnosis can still be confirmed by keeping a peak expiratory flow (PEF) diary for 2-4 weeks to document diurnal variability; if possible, perform a bronchoprovocation test after discontinuing bronchodilators according to the guidelines. This is especially appropriate for "difficult to diagnose" dyspnea. [2]

In adults and adolescents, the diagnosis is best confirmed by spirometry with a bronchodilation test; in children aged 5-11 years, the same methods are used, but PEF diaries and FeNO are more prominent when spirometry is unavailable. In children under 5 years, objective tests are often infeasible: focus is on the typical wheezing phenotype, a trial of treatment, and reassessment upon reaching 5 years of age. [3]

It's important to remember: no single test alone "diagnoses" or "removes" asthma. The decision is a combination of clinical evaluation plus one or more objective tests performed according to standards (preparation, medication discontinuation, proper technique). If in doubt, repeat the tests and/or refer to a specialist. [4]

Objective evidence of variability: spirometry and bronchodilator testing

Spirometry - Test #1: The initial decline in FEV₁/VC (or FEV₁/FVC) is recorded and the effect of a short-acting β₂-agonist is assessed (usually 400 mcg salbutamol, wait 15 minutes). The classic “positive” response is an increase in FEV₁ ≥12% and ≥200 ml from baseline; the joint ATS/ERS 2022 standard allows an alternative criterion of “>10% predicted”. The higher the response, the higher the likelihood of asthma. [5]

If baseline values are normal but clinical findings are compelling, repeat spirometry during symptomatic periods or after discontinuing bronchodilators to capture variability. It is also acceptable to test FEV₁ variability on different days: fluctuations of ≥12% often support the diagnosis in typical clinical settings. All of this should be performed according to technical standards (quality of maneuvers, calibration, reference values). [6]

Some patients show a response in FVC (an increase of ≥12% and ≥200 ml) in the absence of a significant increase in FEV₁. This also qualifies as a positive bronchodilator response, especially if there is clinical and/or other evidence of variability. In real-world practice, combine spirometry with a PEF and/or FeNO diary. [7]

If bronchodilation is not demonstrated, this does not rule out asthma: in controlled patients or on an asymptomatic day, spirometry may be normal. Then, a PSV diary and/or provocative tests are used, and "enemies of diagnosis" are reviewed: recently taken bronchodilators, incorrect technique, and intervals between doses. [8]

Variability of PSV and bronchoprovocation tests

Home monitoring of PEF for 2-4 weeks, with calculation of the daily amplitude (morning-evening), is an affordable way to confirm variability. The diagnosis is supported by an average daily PEF variability of ≥10% in adults (≥13% in children), as well as an increase in PEF of ≥20% after bronchodilator therapy. The more stable the technique and the more regular the recordings, the more reliable the conclusion. [9]

When a definitive test of hyperreactivity is needed, methacholine or mannitol bronchodilator challenge is performed. For methacholine, a PC₂₀ ≤8 mg/mL (or PD₂₀ ≤200 μg) is considered "positive"—this indicates hyperreactivity compatible with asthma (not specific, but sensitive). Mannitol is "positive" if PD₁₅ ≤635 mg cumulative dose. [10]

A negative methacholine test is highly likely to exclude current asthma in symptomatic patients if the test is performed correctly (adequate drug withdrawal and technique). However, false-negative results are possible in remission, with high doses of inhaled steroids, or in elite athletes. [11]

Before the challenge, withdrawal windows are strictly observed: SABA ≥6 hours, long-acting β₂-agonists up to 48 hours (depending on the molecule), and theophylline – longer. The study is conducted according to the ERS standard with safety monitoring and discontinuation criteria. [12]

Airway inflammation biomarkers (FeNO, peripheral blood, sputum)

Exhaled nitric oxide (FeNO) reflects eosinophilic/type-2 inflammation. According to the ATS guidelines: in adults, ≥50 ppb is a high level, increasing the likelihood of asthma and response to inhaled steroids; <25 ppb is a low probability of an eosinophilic component. In children, the corresponding thresholds are lower (≈35 and ≈20 ppb). Interpretation is always contextual (smoking, atopy, infections). [13]

In national pathways (BTS/NICE/SIGN), FeNO is included in the first line of objective tests in adults and some children aged ≥5 years, which improves the accuracy of early diagnosis. GINA 2024 confirms the usefulness of FeNO for confirming asthma and selecting for anti-inflammatory therapy, although the test alone does not make a diagnosis. [14]

Blood eosinophils (e.g., ≥0.3×10⁹/L) support the type 2 phenotype and risk of exacerbations, but do not by themselves diagnose asthma (other causes of eosinophilia are possible). Induced sputum with eosinophils ≥2-3% increases the likelihood of eosinophilic asthma, but this method is not available everywhere. Use these indicators as "boosters" of probability in conjunction with functional tests. [15]

Combinations of "clinical + FeNO + bronchodilator response/PEF variability" provide the best diagnostic accuracy in outpatient practice. If discrepancies occur, repeat measurements, change the time of day/conditions, and check the technique before drawing final conclusions. [16]

Visualization, other studies and why they are needed

Chest X-rays and CT scans do not confirm asthma but help rule out alternatives (foreign body, tumor, bronchiectasis, chronic infection). They should be considered for atypical presentations (unilateral wheezing, systemic symptoms, hemoptysis), atypical onset after age 40-50, or poor response to treatment. [17]

Pulse oximetry and exercise testing are useful for assessing hypoxemia and associated dysfunction (due, for example, to obesity or deconditioning), but are not specific for asthma. Their role is risk stratification and rehabilitation planning. [18]

Allergy testing (prick tests/IgE to inhalant allergens) does not "diagnose" asthma, but it does confirm the underlying atopic pattern, identify triggers, and aid in phenotyping. This is especially valuable in children and young adults. [19]

In “difficult” cases, plethysmography (volumes, resistance), oscillometry in children and the elderly, and exhaled NO according to the zonal principle are used to clarify the mechanics of the respiratory tract; these methods are a supplement to, but not a replacement for, the basic criteria. [20]

Special groups: children, elderly, pregnant women, athletes

Children <5 years: Absence of reproducible spirometric maneuvers is normal. Diagnostic pathway: clinical suspicion (wheezing episodes, atopy, family history), trial of ICS/anti-leukotriene therapy followed by re-evaluation and attempt of objective tests at age 5 years. Remember to exclude bronchiolitis, aspiration, cystic fibrosis, and malformations. [21]

Children aged 5 years and older and adolescents: spirometry with bronchodilation is possible; FeNO and PEF diaries improve accuracy. If in doubt, refer for provocation or to a specialized pulmonologist/allergist. [22]

Elderly: high prevalence of comorbid COPD, heart failure, and vocal fold dysfunction. A series of timed tests and a bronchodilator test on a "symptomatic" day are often required; consider polypharmacotherapy and maneuverability. [23]

Athletes and pregnant women: Athletes often present with predominantly exercise-induced symptoms with normal spirometry; provocation (mannitol/exercise) and FeNO are helpful. During pregnancy, diagnostic principles are the same, with priority given to safe tests (spirometry, PEF, FeNO), and imaging only when strictly indicated. [24]

Differential diagnosis and when to refer to a specialist

What appears to be asthma is often vocal fold dysfunction, chronic cough syndrome, upper lobe emphysema, heart failure, GERD, tracheobronchomalacia, or eosinophilic bronchitis without obstruction (sputum eosinophils are present, but bronchial obstruction and variability are not). A bronchodilator test, PEF variability, provocation, and FeNO can help differentiate these conditions. [25]

Refer to a specialist if: the diagnosis remains in doubt after two objective attempts; tests are inconsistent with the clinical picture; there are red flags (hemoptysis, single unilateral crackles, systemic symptoms, weight loss), or if bronchoprovocation/induced sputum is required. [26]

If comorbidities are suspected (e.g. COPD-asthma overlap), the logic is the same: first confirm flow variability (BP response, PEF), then phenotype inflammation (FeNO, eosinophils) and only then adjust long-term therapy. [27]

Remember: seemingly "resistant" asthma is often unproven. GINA recommends re-diagnosis in anyone receiving high-dose ICS or biologic therapy without objective evidence of asthma. [28]

Typical mistakes and working algorithm

Mistake #1 is making a diagnosis without objective tests ("by whistles alone") or, conversely, denying asthma based on a single normal spirometry result. The solution is repeat measurements and alternative evidence of variability. [29]

Mistake #2 – Violation of standards: failure to discontinue bronchodilators, poor technique, incorrect reference values. This reduces sensitivity/specificity and leads to errors. Follow ATS/ERS technical documents on spirometry and provocative testing. [30]

Mistake #3: Retesting with a single method (e.g., only FeNO) or relying on a single threshold. Always combine clinical testing with several independent tools: spirometry ± BD test, PSV diary, FeNO, provocation—depending on the situation. [31]

Working algorithm: 1) clinical probability is high → 2) spirometry + BD test → 3) if inconclusive - PSV diary/FeNO → 4) if necessary - methacholine/mannitol → 5) in case of contradictions or “red flags” - visualization, extended search for alternatives and referral to a specialist. [32]

Tables

Table 1. Objective evidence of variable flow limitation (adults/adolescents)

Criterion	Threshold	Comment
Bronchodilator response by FEV₁	≥12% and ≥200 ml of the initial, or >10% of the expected	Perform as standard, 400 mcg salbutamol, 15 min wait. [33]
Variability of PSV (2-4 weeks)	Average daily variability ≥10%	Reliability ↑ with good technique and regularity. [34]
PEF response to bronchodilator	Growth ≥20%	Quick cabinet indicator. [35]
Bronchoprovocation (methacholine)	PC₂₀ ≤8 mg/ml or PD₂₀ ≤200 mcg	High sensitivity, low specificity. [36]

Table 2. FeNO: how to interpret

Group	Low	Borderline	High
Adults	<25 ppb	25-50 ppb	>50 ppb
Children	<20 ppb	20-35 ppb	>35 ppb
Clue	Low probability of T2 inflammation; look for other causes	Interpret in context	High probability of T2 asthma and response to ICS

Table 3. Bronchoprovocation tests: thresholds

Test	"Positive" result	Note
Methacholine	PC₂₀ ≤8 mg/ml (or PD₂₀ ≤200 mcg)	Discontinue bronchodilators early.[37]
Mannitol	PD₁₅ ≤635 mg (cumulative)	Useful for exercise-induced symptoms. [38]

Table 4. When to test for asthma first (besides clinical examination)

Situation	What to do immediately	For what
An adult with a convincing clinical picture	Spirometry + BD test; FeNO	Rapidly confirm the diagnosis and T2 phenotype. [39]
Normal spirometry, but symptoms	PSV diary 2-4 weeks; consider provocation	Capturing Variability. [40]
Relapses under load	Mannitol/load test	Verify the EIB phenotype. [41]
Children 5-11 years old	Spiro + BD, FeNO/PSV according to availability	Increase accuracy without excessive radiation exposure. [42]

Table 5. Asthma Red Flags (Look for an Alternative)

Sign	Opportunity	Action
Unilateral persistent wheezing, hemoptysis	Foreign body, tumor	Imaging/bronchoscopy. [43]
Lack of any objective evidence of variability across multiple trials	Non-asthma (VCD, COPD, EBD)	Provocation, ENT examination, spirometry repeats. [44]
Late onset with systemic symptoms	Oncopathology, vasculitis	Advanced diagnostics/referral. [45]