Diagnostic value of outcome measures following allergen exposure in an environmental challenge chamber compared with natural conditions.
BACKGROUND
Efficacy testing of drugs in seasonal allergic rhinitis (SAR) is often disturbed by seasonal variations of environmental allergens, and assessment of onset and duration of action is hardly possible under natural conditions. Allergen provocation in an environmental challenge chamber (ECC) can be of added value in this respect. However, the specificity, sensitivity, and reproducibility of outcome measures under both settings are unclear.


OBJECTIVE
The aim of this study was to investigate and compare the diagnostic value (specificity, sensitivity, and reproducibility) of clinical end-points and biomarkers both following allergen provocation in an ECC and under natural conditions.


METHODS
Sixty adult patients with SAR to grass and 60 healthy subjects were exposed twice to grass pollen in an ECC and observed twice during the pollen season. Symptoms, nasal flow, as well as exhaled and nasal nitric oxide (NO) were investigated.


RESULTS
The total nasal symptom score (TNSS) in the ECC had the best reproducibility (intraclass correlation coefficient ICC=0.86) and sensitivity/specificity [area under receiver operating characteristic curve (AUC)=0.99] of all measures. Symptoms in season also had good sensitivity/specificity but were far less reproducible. Nasal flow in the ECC had good sensitivity/specificity but reproducibility was limited. NO measurements showed good reproducibility but sensitivity/specificity were limited, except for exhaled NO in season (AUC=0.75).


CONCLUSIONS
The high reproducibility and sensitivity/specificity in the ECC suggests that TNSS is a valuable outcome measure. While exhaled NO can be considered to monitor airway inflammation, nasal NO appears to be unspecific.
Hohlfeld
J M
JM
Department of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany. jens.hohlfeld@item.fraunhofer.de
Holland-Letz
T
T
Larbig
M
M
Lavae-Mokhtari
M
M
Wierenga
E
E
Kapsenberg
M
M
van Ree
R
R
Krug
N
N
Bufe
A
A
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D015203:Reproducibility of Results; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis*; D012680:Sensitivity and Specificity
D015415:Biomarkers; D009569:Nitric Oxide