Methacholine challenge: test-shortening procedures.

STUDY OBJECTIVES: Validation of test-shortening procedures for the 2-min tidal breathing methacholine challenge method. DESIGN: Retrospective chart review. SETTING: Tertiary-care university clinical pulmonary function laboratory. PATIENTS: One thousand subjects aged 10 to 85 years (mean +/- SD, 44.5 +/- 16.0 years), 44.5% male, referred for methacholine challenge. INTERVENTION: Two-minute tidal breathing methacholine challenge was performed, with both physician and technician access to published test-shortening procedures. MEASUREMENTS AND RESULTS: There were 315 positive test results (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] < or = 8 mg/mL) and 685 negative test results. The subjects with positive test results were less likely to be male (39.1 vs 47.5%; p < 0.02) and had lower FEV(1) (91.8 +/- 14.9% predicted vs 97.2 +/- 13.9% predicted; p < 0.001). The average starting PC(20) was between 0.5 mg/mL and 1.0 mg/mL; the most common PC(20) was 1 mg/mL (67%). There were 431 skipped concentrations in 380 subjects. The mean number of methacholine inhalations was 3.7 +/- 1.1 (3.9 +/- 0.1 for negative test results vs 3.3 +/- 1.2 for positive test results; p < 0.001). Eighteen subjects had a > or = 20% FEV(1) fall on the first inhalation, and 11 subjects had a > or = 20% FEV(1) fall after a skipped concentration. In only one case (0.1%) an FEV(1) fall > or = 40% on the first concentration was reported, compared with no cases after a skipped concentration and seven cases with a > or = 40% FEV(1) fall after a routine doubling dose step-up. CONCLUSIONS: The 2-min tidal breathing methacholine test in clinical practice can be safely shortened to an average of less than four inhalations using starting concentrations based on FEV(1), asthma medication, and clinical features, and by occasionally omitting concentrations.

Twice weekly isoniazid and rifampin treatment of latent tuberculosis infection in Canadian plains Aborigines.

Six months of twice weekly directly observed isoniazid and rifam-picin treatment of latent tuberculosis (TB) infection was implemented to improve the outcome of treatment. A total of 591 infected aborigines without previous tuberculosis or treatment of latent TB infection received twice weekly isoniazid and rifampicin for 6 mo from 1992 to 1995. The outcome was compared with 403 infected aborigines without previous tuberculosis or treatment of latent TB infection who received self-administered isoniazid daily for 1 yr from 1986 to 1989. Of patients, 487 (82%) completed the twice weekly 6-mo regimen compared with 77 (19%) who completed the daily 12-mo regimen. The main reason for incomplete treatment was default. Both groups were followed over a 6-yr period. The rate of tuberculosis in the twice-weekly isoniazid and rifampicin-treated patients was 0.9/1,000 patient-years compared with 9/1,000 patient-years in the daily isoniazid-treated patients. The rate of side effects was higher for directly observed treatment patients, 136/1,000 patient-years of drugs, compared with 39/ 1,000 patient-years for self-administered treatment patients. Life-threatening side effects such as skin allergic reactions and hepatitis were the same in both groups. A regimen of 52 doses of directly observed twice weekly isoniazid and rifampicin is an effective and well-tolerated regimen to improve the outcome of the treatment of latent tuberculosis infection in a population with a high rate of default with daily self-administered isoniazid.

Detection of pulmonary tuberculosis in patients with a normal chest radiograph.

OBJECTIVES: To describe the early symptoms of pulmonary tuberculosis (TB) when the chest radiograph (CXR) is normal. SETTING: Centralized, provincial TB control program. SUBJECTS: Twenty-five patients with culture-positive pulmonary TB and a normal CXR were identified from a review of 518 consecutive patients with culture-positive pulmonary TB in the province of Saskatchewan from January 1, 1988 to March 31, 1997. Patients with abnormal CXRs at the time of diagnosis were excluded from the analysis. RESULTS: Twenty-three of the 25 patients (92%) were symptomatic at the time of diagnosis, with cough/sputum (76%) being reported most commonly. Eleven patients were identified because of contact tracing from cases of infectious pulmonary TB, while the other 14 patients were identified because of an investigation of symptoms. Twenty-four patients (96%) exhibited one or more symptoms of cough for > 1 month, fever for > 1 week, or skin-test conversion after contact with infectious TB. The sputum smear of only one patient was positive. Two patients were pregnant at the time of diagnosis, one patient was HIV-positive, and one patient demonstrated isoniazid-resistant organisms on sensitivity testing. Five patients were diagnosed as having primary TB associated with Mantoux skin-test conversion. The incidence of culture-positive pulmonary TB with a normal chest radiograph was < 1% in the period from 1988 to 1989 and steadily increased to 10% in the period from 1996 to 1997. CONCLUSIONS: Culture-positive pulmonary TB with a normal CXR is not uncommon, and the incidence of this presentation is increasing. Patients with this presentation of TB are typically symptomatic and/or are detected by contact tracing to infectious cases of pulmonary TB. The results suggest that patients presenting with a cough for > 1 month, with a fever for > 1 week, or with documented skin-test conversion < 2 years after known exposure to infectious TB should have sputum submitted for a Mycobacterium tuberculosis smear and culture despite a normal CXR.