Asthma is characterized by airway inflammation, airway hyper-responsiveness (AHR) and variable air flow obstruction. The diagnosis of asthma, however, is often based upon nonspecific clinical symptoms of cough, wheeze, and shortness of breath. Furthermore, the physical examination and measurements of pulmonary function are often unremarkable in patients with asthma, thereby complicating the diagnosis of the disease. The following discussion will review approaches to the diagnosis of asthma when lung functions are normal, and will largely focus on the use of bronchial provocation tests to detect underlying AHR.
BusseWW, LemanskeRFJr. Asthma. N Engl J Med, 2001; 344(5):350–362..
2.
MooreWC, MeyersDA, WenzelSE, TeagueWG, LiH, LiX, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med, 2010; 181(4):315–23..
3.
Platts-MillsT, VaughanJ, SquillaceS, WoodfolkJ, SporikR. Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet, 2001; 357(9258):752–756..
4.
BusseWW. The relationship of airway hyperresponsiveness and airway inflammation: airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest, 2010; 138(2 Suppl):4S–10S..
National Heart Lung and Blood Institute. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma - full report 2007. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed October 31, 2011..
BatemanED, BousheyHA, BousquetJ, BusseWW, ClarkTJ, PauwelsRA, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med, 2004; 170(8):836–844..
9.
Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management Program Research Group. N Engl J Med, 2000; 343(15):1054–1063..
10.
WenzelSE, BusseWW. Severe asthma: lessons from the Severe Asthma Research Program. J Allergy Clin Immunol, 2007; 119(1):14–21..
American Association for Respiratory Care. Clinical Practice Guideline. Methacholine challenge testing: 2001 revision & update. Respir Care, 2001; 46(5):523–530..
13.
SontJK, WillemsLN, BelEH, Van KriekenJH, VandenbrouckeJP, SterkPJ. Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. Am J Respir Crit Care Med, 1999; 159(4 Pt 1):1043–1051..
AndersonSD, CharltonB, WeilerJM, NicholsS, SpectorSL, PearlmanDS; A305 Study Group. Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma. Respir Res, 2009; 10:4..
16.
CockcroftDW. Direct challenge tests: airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest, 2010; 138(2 Suppl):18S–24S..
17.
BarnesPJ, DweikRA, GelbAF, GibsonPG, GeorgeSC, GrasemannH, et al. Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest, 2010; 138(3):682–692..
18.
MalmbergLP, PelkonenAS, HaahtelaT, TurpeinenM. Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma. Thorax, 2003; 58(6):494–499..
19.
DeykinA, MassaroAF, DrazenJM, IsraelE. Exhaled nitric oxide as a diagnostic test for asthma: online versus offline techniques and effect of flow rate. Am J Respir Crit Care Med, 2002; 165(12):1597–1601..
20.
JatakanonA, LimS, KharitonovSA, ChungKF, BarnesPJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax, 1998; 53(2):91–95..
21.
SmithAD, CowanJO, FilsellS, McLachlanC, Monti-SheehanG, JacksonP, et al. Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests. Am J Respir Crit Care Med, 2004; 169(4):473–478..
22.
NairP, PizzichiniMM, KjarsgaardM, InmanMD, EfthimiadisA, PizzichiniE, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med, 2009; 360(10):985–993..
23.
HaldarP, BrightlingCE, HargadonB, GuptaS, MonteiroW, SousaA, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med, 2009; 360(10):973–984..
24.
O'ByrnePM, GauvreauGM, BrannanJD. Provoked models of asthma: what have we learnt?. Clin Exp Allergy, 2009; 39(2):181–192..
25.
LeuppiJD, TandjungR, AndersonSD, StolzD, BrutscheMH, BingisserR, et al. Predition of treatment-response to inhaled corticosteroids by mannitol-challenge test in COPD. A proof of concept. Pulm Pharmacol Ther, 2005; 18(2):83–88..
26.
PearlmanD. A phase III multicenter study to demonstrate the sensitivity and specificity of Aridol (mannitol) challenge to predict bronchial hyper-responsiveness as manifested by a positive exercise challenge in subjects presenting with signs and symptoms suggestive of asthma but without a definitive diagnosis. http://clinicaltrials.gov/ct2/show/NCT00252291. Accessed September 26, 2011..
27.
CockcroftDW, DavisBE, ToddDC, SmycniukAJ. Methacholine challenge: comparison of two methods. Chest, 2005; 127(3):839–44..
28.
BrasierAR, VictorS, JuH, BusseWW, Curran-EverettD, BleeckerE, et al. Predicting intermediate phenotypes in asthma using bronchoalveolar lavage-derived cytokines. Clin Transl Sci, 2010; 3(4):147–157..
