A Comparative Bronchial Provocation Study With Mannitol and Methacolinie in a Korean Population
Condition: Asthma
Study type: Interventional

Summary: 
      Asthmatic patients and non-asthmatic controls were recruited prospectively from four referral
      hospitals in Korea. Participants were challenged with each of methacholine and mannitol
      inhalation on different days. Their diagnostic utility was evaluated by calculating their
      sensitivity and specificity for asthma diagnosis. Response-dose-ratio was also compared.
    

Detailed description: 
      This study was a prospective, multicenter study performed at four referral hospitals in
      Korea: Seoul National University Hospital, Samsung Medical Center, Ajou University Hospital,
      and Hanyang University Medical Center. Hospital-based recruitment was performed for asthmatic
      patients and non-asthmatic controls. Asthmatic patients were defined as those who had been
      diagnosed with asthma by specialist physicians; they had recurrent symptoms of asthma
      (wheezing and dyspnea) and used anti-asthmatic medication for 6 months before the enrollment.
      Non-asthmatic controls were voluntarily recruited from hospital visitors; they were included
      if they had never wheeze or physician diagnosed asthma.

      Common inclusion criteria were Korean adults between the age of 18 and 70 years who could
      understand and perform lung function tests and bronchial challenges. Exclusion criteria were
      any one of following: history of recent respiratory infection (within the last 4 weeks),
      history of a recent surgery, history of heart disease that could impose risks during
      bronchial challenges, history of uncontrolled hypertension, current smokers or ex-smokers
      with more than 10 pack-years, history of known pulmonary diseases with the exception of
      asthma, pregnancy or lactation, severe obesity (body mass index [BMI] of >35 kg/m2), history
      of any health condition considered inappropriate for participation in this study, or a
      pre-bronchodilator predictive value of forced expiratory volume in 1 second (FEV1) of <70%.

      All participants underwent methacholine bronchial challenge test and mannitol challenge test
      on different days, separated by least 24 h, as in previous reports.7, 10 All asthmatic
      patients stopped their anti-asthma medications before the tests according to the
      predetermined protocols. The protocol was approved by the Institutional Review Board of Seoul
      National University Hospital. All subjects gave written informed consent.

      Methacholine challenge test> The methacholine challenge test was performed as previously
      described.11, 12 Pulmonary function testing was carried out using a spirometry system
      (SensorMedics 2130; SensorMedics, CA, USA). The methacholine challenge test was performed
      using the Chai method13 with minor modifications. Briefly, methacholine was prepared at the
      following concentrations, diluted with saline: 0.25, 0.625, 1, 4, 16, and 25 mg/mL.
      Methacholine was delivered as an aerosol by a Rosenthal-French dosimeter (Laboratory for
      Applied Immunology, Inc., Baltimore, MD) and a nebulizer. Subjects were instructed to inhale
      five inspiratory capacity breaths while increasing the methacholine concentration from 0.25
      to 25 mg/mL. The methacholine concentration that caused a 20% decrease in the FEV1 from
      baseline was defined as PC20. AHR was defined as positive at PC20 < 16 mg/mL.

      Mannitol challenge test> A commercial mannitol (Aridol™; BL&H Co., Ltd., South Korea) kit was
      used, and the challenge test was performed according to the manufacturer's protocols.14 The
      mannitol capsule dose started at 0 mg and increased to a total cumulative dose of 635 mg.
      Each capsule was placed in the inhalation device, and a hole was made by pressing the device
      button before inhalation. After a deep breath of mannitol, the FEV1 was measured after 60
      seconds. The test was considered positive if the FEV1 value decreased by more than 15%
      compared with the baseline FEV1. The cumulative mannitol dose that caused a 15% decrease in
      the FEV1 from baseline was defined as PD15. If the FEV1 did not decline by more than 15%, the
      dose was increased until a cumulative dose of 635 mg was reached. If the FEV1 did not fall by
      more than 15% until the last dose, the test was considered negative.
    

Intervention name(s): methacholine and mannitol bronchial challenge tests
Intervention type(s): Procedure
Intervention description(s): Airway hyperresponsiveness is a common feature of asthma. Methacholine and mannitol are two representative agonists for bronchial challenge. They have theoretically different mechanisms of action, and may have different diagnostic properties. However, their difference has not been directly evaluated among Korean adults. In this study, we compare the diagnostic properties of methacholine and mannitol bronchial provocation tests.
Asthmatic patients and non-asthmatic controls were recruited prospectively from four referral hospitals in Korea. Participants were challenged with each of methacholine and mannitol inhalation on different days. Their diagnostic utility was evaluated by calculating their sensitivity, specificity, positive/negative predictive values for asthma diagnosis.
Intervention MeSH terms: Mannitol; Methacholine Chloride
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Bronchial provocation test; Mannitol; Methacholine; Bronchial hyperreactivity; Sensitivity and specificity