Table 2.

Proposed algorithm of diagnosis of AERD. The diagnosis of AERD is a major challenge in patients suffering from CRS with/without nasal polyps, bronchial asthma, and/or unknown underlying diseases. The diagnostic approach of AERD is based on the clinical picture. This might be supported by imaging as well as in vitro techniques. The confirmative diagnosis for AERD is definitely established by aspirin challenge following increasing doses of aspirin. The routes of administration are (1) oral, (2) bronchial inhalation, (3) nasal inhalation, and (4) intravenous. Nasal or bronchial obstruction has to be monitored adequately. Provocation must be performed only when asthma is stable and is precluded on ethical grounds, unstable asthma, asthma nonresponsive to corticoids, or patients on β-blockers. Aspirin challenge tests should be performed by trained specialist in centres with the availability of adequate equipment and medication for emergency.

Diagnostic procedure of AERD
Prior to aspirin challenge
(1) Medical history	(i) Individual history
	(ii) Family history
(2) Severity of symptoms (suspected from historical reactions)	(i) No
	(ii) Mild
	(iii) Moderate
	(iv) Severe
(3) Class of NSAID	(i) Strong COX-1 inhibitors
	(ii) Poor COX-1 inhibitors
	(iii) Preferentially COX-2 inhibitors
	(iv) Selective COX inhibitors
(4) Physical examination  (a) Localisation of symptoms  (b) Stable asthma	(i) Airways
	(ii) Skin
	(iii) Gastrointestinal tract
	(iv) Other organs
	(v) FEV1 >70% and with 10% of best prior value
(5) Medication  (a) Drug responsiveness  (b) Actual medication	(i) Asthma responsiveness to corticoids
	(ii) Systemic/topic corticoids
	(iii) β-blockers
	(iv) Antihistamines
	(v) Others
Patient selection for aspirin challenge
(1) Suspected reactions	(i) Mild-to-moderate prior historical reactions
(2) Responsiveness to drugs	(ii) Responsiveness to corticoids, leukotriene modifiers, β-blockers
(3) Anatomical alterations	(iii) No aggressive polyp formation
(4) Compliance of patient	(iv) In need of daily aspirin
(5) Pretreatment	(v) Continuing of all medications for upper and lower airways, including inhaled an intranasal corticosteroids
	(vi) Leukotriene modifier drug 2–4 weeks prior to (in case of safety reasons)
Aspirin challenge
In vivo provocation according to an appropriate protocol	(i) Determination of airway stability (FEV1 >70%, 10% variability, every 1–3 h)
	(ii) Discontinue antihistamines 48 h before challenge
In vitro challenge, in case of	(i) Unstable asthma
	(ii) Unresponsiveness to corticoids
	(iii) Anatomical alterations
	(iv) Ethical grounds
	(v) Unavailability of technical and/or medical equipment
	(vi) In cases of non-airway-related symptoms and those not becoming obvious upon in vivo aspirin challenge
Treatment of aspirin-induced reactions
Ocular Nasal Laryngeal Bronchial Gastrointestinal Urticaria/angioedema Hypotension	(i) Topical antihistamines
	(ii) (Oral) antihistamines or diphenhydramine, topical decongestant
	(iii) Racemic epinephrine nebulization
	(iv) Inhalation of β-agonist every 5 minutes until confortable
	(v) Empting
	(vi) Intravenous ranitidine
	(vii) Intravenous diphenhydramine
	(viii) Epinephrine administered intramuscularly