a 30-year - old caucasian man presented to the pulmonary function laboratory for a pulmonary function test ( pft ) and methacholine challenge test .
measured height and weight on the day of testing indicated a body mass index of 28.1 kg / m .
baseline pft data are summarized in table 1 , the flow - volume loop and volume - time curve from spirometry are shown in figure 1 . all testing satisfied american thoracic society ( ats)/european respiratory society acceptability and repeatability quality standards ( 1 ) .
baseline spirometry suggested a restrictive ventilatory defect , which was confirmed by lung volume measurements via whole body plethysmography . following baseline testing ,
a methacholine challenge test was performed using the five - breath dosimeter technique ( 2 ) . following inhalation of the final dose of methacholine ( 20 mg / ml ) , the forced expiratory volume in 1 s ( fev1 ) was 8% below baseline .
negative methacholine challenge test ; however , the patient complained of chest tightness and dyspnea .
the patient s symptoms in the absence of a significant decline in fev1 prompted repeat measurement of specific airway conductance ( sgaw ) as an alternative method to assess the airway response to methacholine inhalation .
the sgaw was found to be 73% below baseline , indicating significant airway narrowing compatible with marked airway hyper - responsiveness .
following bronchodilator administration ( 2.5 mg albuterol via small volume nebulizer ) both the fev1 and sgaw values were larger than those recorded during baseline testing , suggesting a degree of pretest bronchoconstriction ( table 2 , figure 2 ) .
the 1999 ats guideline for methacholine challenge testing states that fev1 should be the primary outcome measure for the discovery of airway hyper - responsiveness ( 2 ) .
the guideline recognizes that alternative measures of pulmonary function ( eg , sgaw , impulse oscillometry ) may be used during a methacholine challenge test ; however , these measures are recommended only when the patient can not produce high - quality spirometry data . a whole - body plethysmograph ( often called a  body box )
the patient is asked to breathe small volumes at a rate of 1.5 breaths / s to 2.5 breaths / s .
flow at the mouth is plotted against the pressure inside the plethysmograph ( ie ,  box pressure ) . after the collection of several breaths ,
a shutter or valve is closed so that mouth ( alveolar ) pressure can be plotted against box pressure .
this is accomplished by having the patient continue shallow breathing at a rate of approximately 1 breath / s .
following open and closed shutter breathing , mouth pressure can be divided by flow to calculate airway resistance .
sgaw is considered to be a more useful value because it represents the conductance adjusted to the lung volume where the measurement was recorded . in other words ,
the ats guideline recommends that a larger reduction in sgaw ( eg , 45% ) be used as a cut - off point for a
khalid et al ( 3 ) evaluated sgaw and fev1 in 138 patients undergoing a methacholine challenge test .
the researchers found that a 51% to 52% reduction in sgaw was a more appropriate cut - off point for a positive methacholine challenge test than the 45% reduction suggested by the ats .
a remarkable finding was that 32 patients with an fev1 decline < 20% exhibited a reduction in sgaw > 50% .
in a similar study , parker and mccool ( 4 ) measured fev1 and sgaw following methacholine challenge testing in 248 consecutive patients with asthma - like symptoms .
forty patients showed a response to methacholine as assessed by sgaw ( 40% reduction ) without a significant decline in fev1 ( < 20% ) .
the obvious question that arises from these observations is whether using fev1 as the sole outcome measure during methacholine challenge testing results in false - negative tests in some patients . in other words , does the positive sgaw / negative fev1 response indicate asthma or an expected response in some nonasthmatic patients or both ?
parker and mccool ( 4 ) found that subjects with this response had a higher baseline sgaw and forced expiratory flow between 25% and 75% of the forced vital capacity ( fef2575 ) to forced vital capacity ratio , suggesting that dysanapsis ( large tracheobronchial tree compared with lung size ) may be causal .
the authors offered other possible mechanisms for the positive sgaw / negative fev1 response including disproportionate proximal airway narrowing , differences in airway compliance and airway smooth muscle distribution .
both studies used the five - breath dosimeter technique with inhalation of aerosol to total lung capacity .
cockcroft and davis ( 5 ) showed that this technique results in false - negative methacholine challenge tests as judged by fev1 in patients with mild asthma .
it is not clear whether sgaw and fev1 are equally affected by the bronchodilatory and bronchoprotective effects of deep inhalation .
in addition to nonspecific airway challenge testing ( eg , methacholine , histamine ) , larbanois et al ( 6 ) reported that 13% of patients undergoing specific inhalation challenge had a 50% decline in sgaw without a 20% decline in fev1 . because sgaw is believed to be more reflective of large airway function ( 7 ) , the authors speculated that this pattern may , in part , be related to the site of aerosol deposition .
given the complexity of pulmonary structure and function in the realm of airway hyper - responsiveness ( 8) , the etiology of the positive sgaw / negative fev1 response is likely multifactorial .
whether one chooses to follow fev1 , sgaw or both , the inherent limitations of bronchial challenge tests must be appreciated to avoid misinterpretation and misdiagnosis .
methacholine challenge tests are not perfect , the sensitivity and specificity can be < 60% and 70% , respectively ( 9 ) .
methacholine challenge tests simply determine the presence of airway hyper - responsiveness to a nonspecific agent .
the presence of airway hyper - responsiveness only increases the probability of asthma in patients with an intermediate or high pretest probability of asthma ( 10 ) .
it would also be incorrect to assume that every patient with a positive sgaw / negative fev1 response to methacholine challenge testing has asthma
. this would be especially suspect in patients with a low pretest probability of asthma . in the present case , however , the patient had an intermediate pretest probability of asthma due to his asthma - like symptoms and family history .
the fact that the large reduction in sgaw during methacholine challenge testing was accompanied by familiar symptoms that he had experienced after exercise increases the post - test probability of asthma , even in the absence of a 20% reduction in fev1 .
 methacholine challenge tests only determine airway hyper - responsiveness to a nonspecific agent , and can be associated with relatively low sensitivity and specificity ; therefore , they should not be used in isolation to diagnose asthma . accordingly , alternative adjunctive measures of pulmonary function have been recommended in cases in which an individual can not produce high - quality spirometry data . 
 this report describes a case involving a 30-year - old man with a primary complaint of dyspnea with exercise . 
 the ensuing discussion briefly reviews these alternative measures and the inherent limitations of the methacholine challenge test . 
CASE PRESENTATION
DISCUSSION