Role of Cigarette Smoking in Regulating Allergen-induced Early and Late Responses in Mild Asthmatics
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The objective of this study is to determine the effect of cigarette smoking on inflammatory
      cell recruitment to the lungs after an allergen challenge, in non-smoking and currently
      smoking mild asthmatic subjects.

      When comparing non-smoking asthmatics to smoking asthmatics, do differential cell counts
      obtained from inflammatory cells in induced sputum after allergen challenge differ?

      Will differential cell counts show a decline in inflammatory cells in the induced sputum of
      asthmatics who have refrained from smoking for eight weeks?

      This study is a randomized, case-controlled study. The first part of the study requires
      smoking and non-smoking subjects who will attend 2 study periods of 3 consecutive days
      (triad). In each triad, they will be challenged with allergen or diluent by inhalation, in a
      random order, and each triad is separated by a washout period. In the second part of the
      study, current smokers will be invited to undergo another allergen challenge 8 weeks of
      smoking cessation.
    

Detailed description: 
      10 non-smoking adult subjects and 10 smoking adult subjects with mild atopic asthma will be
      studied.

      Part 1: On the first study day of the triad, subjects will undergo screening procedures,
      including complete history and physical examination. Methacholine inhalation challenge and
      allergen skin titration will be performed to determine the concentration of allergen required
      for inhalation. Sputum will be induced for baseline measurement of airway inflammatory cells.
      On the second day, subjects will inhale the allergen or diluent in randomized order, and
      spirometry will be measured for the next 7 hours. Sputum will be collected at 7 hours after
      challenge. On the third day, subjects will report to the lab 24 hours after allergen/diluent
      inhalation challenge. Sputum cells will be collected to measure the percentage of airway
      inflammatory cells, including eosinophils and neutrophils. After washout of 2-4 weeks,
      subjects will return to undergo diluent/allergen triad.

      Part 2: Asthmatic smokers will be studied to investigate allergen-induced changes in
      inflammatory cell numbers after they quit smoking for a period of 8 weeks. Asthmatic smokers
      who were involved in the first part of the study will be asked if they would like to
      participate in this part of the study, and they will be provided with smoking cessation tools
      including nicorette gum and nicotine patches, to aid them in ceasing to smoke. At the
      beginning of the study period, the same procedures that occurred in part 1 will be performed
      to obtain initial baseline results- ie- history, physical examination, skin prick test,
      methacholine challenge and sputum induction. Throughout the 8 week period, subjects will be
      required to come in weekly to perform a carboxyhemoglobin test, to ensure that they have not
      been smoking that week. At the end of the 8 week period, an allergen challenge triad will be
      carried out (as was performed in Part 1 of the study). Those subjects who were not able to
      comply to the smoking cessation regime will still be included in the final measurements.

      We hypothesize that inflammatory cell counts will be higher in the asthmatic smokers versus
      asthmatic non-smokers. We also hypothesize that subjects who quit smoking for the 8 week
      period will show a decline in inflammatory cell counts indicating an improvement in lung
      function.

      We believe that the results of this novel study will provide greater insight into the
      inflammatory response in asthmatic smokers, and will suggest appropriate therapeutic
      approaches for control of asthma in smokers.
    

Intervention name(s): Allergen Challenge
Intervention type(s): Procedure
Intervention description(s): Allergen challenge
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science
Keywords: smoking; asthma; sputum