We retrospectively analyzed 198 methacholine inhalation challenges (MICs) of symptomatic patients with normal issues of lung examinations.

We retrospectively analyzed 198 methacholine inhalation challenges (MICs) of symptomatic patients with normal issues of lung examinations, spirometry, and chest radiographs. During MIC, five parameters ([FEVsub1] FEF25-75% FVC sGaw, TGV) were measured. Using established changes in these parameters at [les than or equal to] 8 mg/ml methacholine, there were 175 positive proofs (no false positives) and 23 negative exhibitions (15 true negatives, 5 false negatives, and 3 unavailable for follow-up) The MIC sensitivity determined by dint of [FEV.sub.1] responses was significantly lower than the sensitivity using answers in either three ([FEV.sub.1], FEF25-75% and FVC; p [les than] 0001) or five ([FEVsub1] FEF25-75% FVC sGaw, and TGV; p [les than] 0001) parameter settles Sensitivities were 60.6 percent 911 percent and 972 percent respectively. All positive MICs (100 percent) were identified by means of examining changes in the five-parameter place vs 97.3 percent in the three-parameter set; it was a significant difference at p [les than] 001 We judge that the measurement and analysis of non-[FEV.sub.1] parameters in addition to [FEVsub1] significantly increases the sensitivity of the MIC.

Bronchial challenge was first demonstrated in 1910 by dint of Dale and Laidlow[1] in an animal protoplast using histamine as the provocative agent. In man, bronchoprovocative challenges was demonstrated with parenterally administered pilocarpine according to Alexander and Paddock[2] in 1921 while parental histamine was first introduced as a bronchoconstrictive agent by dint of Weiss et al[3,4] in the 1920 In the 1940 curry-powder and Lowell[5-7] used both inhaled and parenteral histamine and methacholine to exhibit obstructive symptoms in normal individuals and make subordinates with hay fever and/or asthma. Subsequently Tiffeneau and Beauvallet[8,9] propos the usefulness of bronchoprovocation testing. However, lacking procedural standardizations and questions regarding safety and specificity, methacholine chloride was not generally adopted as a bronchoprovocation agent for the identification and characterization of hyperreactive airways until the mid 1960s[10] according to 1975, the American Academy of Allergy had published a standard protocol for the administration of a methacholine inhalation challenge (MIC).[11] Rosenthal[12] (1985) has since introduced modifications to this protocol which are now widely accepted.

The accepted benchmark for measuring replys during MIC has been [FEVsub1] We have observ however, that during the course of MIC, a patients demonstrate changes in non.[FEV.sub.1] parameters with or without changes in [FEVsub1] To systematically evaluate the validity of this observation, we retrospectively analyzed 198 consecutive MICs of patients with lower respiratory tract symptoms and normal springs of spirometry. The be the effects of these analyses are at handed in this report.

According to generally accepted guidelines published according to Cropp et al[13] with modifications by means of Rosenthal,[12] an MIC is considered positive when united or more of the following changes offer from the postsaline solution control: 20 percent decrease in [FEVsub1] 25 percent decrease in FEF25-75% 10 percent decrease in FVC 35 to 40 percent decrease in sGaw 25 percent increase in FRC or 25 percent decrease in peak expiratory flowrate. The 8-mg/ml concentration has been propos as an upper limit doorsill concentration of methacholine or histamine for distinguishing asthmatic from nonasthmatic patients.[14-16]

To determine the incidence of positive MICs based in succession changes in [FEV.sub.1] as well as non-[FEV.sub.1] parameters (defined as FEF25-75% FVC sGaw, and thoracic gas tome [TGV]), we retrospectively analyzed 198 consecutive MICs in patients with a history suggestive of asthma still with normal baseline spirometry values. The sensitivities and specificities were determined using rejoinders in [FEV.sub.1] alone, and answers in any one or more of a three-parameter fix ([FEV.sub.1], FEF25-75%, FVC) or five-parameter locate ([FEV.sub.1], FEF25-75%, FVC, sGaw, TGV)

MATERIALS AND METHODS

Subjects

There were 63 male and 136 nonpregnant female patients aged 7 to 75 years with a mean age of 34 years who at handed to a subspecialty practice of allergy and immunology as self-referrals or referrals from primary care physicians. Symptom duration ranged from 3 to 36 month (mean, 5 months) prior to MIC. Those patients who were smoker (n = 40) did not fume at least 12 h prior to MIC. exposing to allergens was not controll There were no patients with late influenza or rubella immunizations. Treatment with medications that could interfere with criterion results was discontinued prior to MIC as follows: theophyllines and antihistamine were withheld for at least 48 h; [[beta].sub.2]-agonist and cromolyn sodium were withheld for at least 12 h Inhaled or oral steroids were continued as requireed Patients were not taking erythromycin, [beta]-blockers, or angiotensin-converting enzyme inhibitors at the time of MIC. Exercise and frontage to cold air were avoided for at least 2 h before the testing. Ingestion of coffee cola, or chocolate drinks was avoided for at least 6 h prior to testing. There were no patients with anemia or polycythemia from CBC determination, chronic bronchitis by way of history, cystic fibrosis (negative sweat chloride), or sarcoidosis (normal chest radiograph, normal lung turn normal angiotensin-converting enzyme level).

...