Symptom evaluation during the methacholine test: Does it add to the interpretation of the test results based on the PC20FEV1?

PURPOSE: Conventionally, symptoms occurring during the methacholine test are not taken into account when interpreting the test results. We examined whether the evaluation of methacholine-induced symptoms (MIS) added to the test interpretation based on the PC20FEV1 by assessing their prevalence, their similarity with symptoms justifying referral and their relationship with airway responsiveness. METHODS: Eighty-two patients with suspected asthma completed a questionnaire of symptoms and underwent bronchial challenge with methacholine. Based on MIS and airway responsiveness (responders = PC20FEV1 < 8 mg/mL), subjects were classified as asymptomatic non-responders (ANRs), asymptomatic responders (ARs), symptomatic non-responders (SNRs) and symptomatic responders (SRs). Airway responsiveness for all subjects, including non-responders (ie, fall in FEV1 < 20%), was assessed by the methacholine concentration response-slope (MCRS) obtained using all points of the curve. RESULTS: ARs (n = 6) were poor-perceivers of bronchoconstriction. SNRs (n = 16) did not differ from SRs (n = 34) in any clinical parameter, including the proportion of subjects (∼80%) whose methacholine test reproduced symptoms justifying referral. In turn, SNRs differed significantly from ANRs (n = 26) by having lower baseline FEV1 (P = .005), more physician-diagnosed asthma (P < .001), more use of respiratory medication (P = .032), and relatively greater responsiveness as manifested by a steeper MCRS (P < .001). CONCLUSIONS: The occurrence of asthma-like symptoms during the methacholine test was associated with milder airway hyperresponsiveness that would go unnoticed by the PC20FEV1. This finding suggests that SNRs should not be merely classified as having normal responsiveness, as currently recommended, but further assessed for airway inflammation. Our results helped planning a longitudinal study to investigate the prognostic validity of this approach.

Does the inclusion of wheeze detection as an outcome measure affect the interpretation of methacholine challenge tests? A study in workers at risk of occupational asthma.

Methacholine challenge testing (MCT) is widely used to assess airway hyperresponsiveness (AHR). Traditionally, a 20% or greater decline in forced expiratory volume in 1 (FEV(1)) is the primary outcome measure. We examined whether the inclusion of wheeze detection as outcome measure influenced the categorical interpretation of MCT in workers at risk of occupational asthma (OA). We examined 28 occupationally exposed smokers with asthma-like symptoms (SympAsth), 22 asymptomatic, occupationally exposed smokers (Symp0), and 30 nonexposed, asymptomatic controls (Ctrl). MCT was done using an abbreviated technique. Spirometry and tracheal wheezes were recorded using a computerized system. MCT was considered either positive or negative using three outcome measures separately: (1) > or = 20% fall in FEV(1) (MCT("FEV1")); (2) wheeze appearance (MCT("Wheeze")); and (3) whichever among the two was present (MCT("FEV1Wheeze")). The proportion of reactors in each group were, by outcome measure, as follows: MCT("FEV1"): Ctrl = 2 (6.7%), Symp0 = 6 (27.3%), SympAsth = l2 (42.8%) (chi(2) = 10.2; p = 0.006); MCT("Wheeze"): Ctrl = 1 (3.3%), Symp0 = 4 (18.2%), SympAsth = 13 (46.4%) (chi(2) = l5.7; p = 0.001); MCT("FEV1Wheeze") Ctrl = 2 (6.7%), Symp0 = 7 (31.8%), SympAsth = 18 (64.3%) (chi(2) = 21.5; p = 0.001). Overall, including wheeze detection increased the proportion of "reactors" detected by spirometry by 30% (27 reactors vs. 20). This increase reached 50% (18 vs. 12) among workers with asthma like symptoms. In summary, the inclusion of wheeze detection as outcome measure for MCT allowed the recognition as reactors of subjects that otherwise would be "missed" by spirometry. The resulting increase in the number of true positives improved the sensitivity of MCT to detect AHR in occupationally exposed workers at risk of occupational asthma.

Smoking cessation--but not smoking reduction--improves the annual decline in FEV1 in occupationally exposed workers.

INTRODUCTION: Individuals exposed both to cigarette smoke and respiratory pollutants at work incur a greater risk of development of airway hyperresponsiveness (AHR) and accelerated decline in forced expiratory volume in 1 s (FEV1) than that incurred by subjects undergoing each exposure separately. We examined whether smoking cessation or smoking reduction improves AHR and thereby slows down the decline in FEV1 in occupationally exposed workers. METHODS: We examined 165 workers (137 males and 28 females) participating in a smoking cessation programme. Nicotine tablets were used for smoking cessation or smoking reduction. Respiratory symptoms were assessed by questionnaire, FEV1 by spirometry and AHR by methacholine challenge test. At 1 year, subjects were classified into quitters, reducers, or continuing smokers. RESULTS: Sixty-seven subjects completed the study (32 quitters; 17 reducers; 18 continuing smokers). Respiratory symptoms improved markedly in quitters (P<0.001 for all comparisons) and less so in reducers (P values between 0.163 and 0.027). At 1 year, FEV1 had slightly but significantly improved in quitters (P=0.006 vs. smokers; P=0.038 vs. reducers) and markedly deteriorated in reducers and continuing smokers. Concurrent, 1-year change in AHR did not differ significantly among the groups. CONCLUSION: In occupationally exposed workers, stopping smoking markedly improved respiratory symptoms and, in males, slowed the annual decline in FEV1. Smoking reduction resulted in smaller improvements in symptoms but deterioration in FEV1. These findings were independent of AHR. While smoking cessation should remain the ultimate goal in workplace cessation programmes more studies are necessary to better ascertain the benefits of smoking reduction.

Nocturnal worsening of asthma and sleep-disordered breathing.

Asthma has a tendency, to destabilize and get worse at night, probably due to a nocturnal increase in airiway inflammation and bronchial responsiveness. Nocturnal airway narrowing in asthma is often associated with sleep disorders, such as episodes of nocturnal and early morning awakening, difficulty in maintaining sleep, and day time sleepiness. On the other hand, an association has been documented between nocturnal sleep-disordered breathing and asthma. This review highlights the causes of nocturnal worsening of asthma and examines the evidence pointing toward a causal relationship between nocturnal asthma and sleep-disordered breathing.