Intranasal CO2 for Allergic Rhinitis
Condition: Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Study type: Interventional

Summary: 
      The purpose of this study is to better understand the way in which CO2 (carbon dioxide)
      affects the symptoms of allergic rhinitis or hayfever.

      Our intent is to determine if CO2 has an effect on nasal challenge with antigen as a
      predictor of whether it will have a beneficial effect on the treatment of seasonal allergic
      rhinitis.
    

Detailed description: 
      Study design: We performed a randomized, two-way crossover study in subjects with seasonal
      allergic rhinitis out of season. Subjects came to the Nasal Physiology Laboratory for
      screening, where they completed an allergy questionnaire and underwent skin-prick testing for
      confirmation of a grass or ragweed allergy. The skin test included positive and negative
      controls and the results were graded compared with the controls as 1+ to 4+ (1+: wheal larger
      than negative control and smaller than positive control; 2+: wheal 5-7 mm; 3+: wheal 7-10 mm;
      4+: any reaction with a wheal >10 mm or pronounced pseudopodia). Subjects with positive skin
      test (between 2+ and 4+) and a positive history of allergic symptoms during the relevant
      seasons then underwent a screening nasal challenge with either grass or ragweed allergen.
      Subjects who passed the screening challenge (twofold increase in either ipsilateral or
      contralateral nasal secretions after allergen challenge compared with diluent) had a 2-week
      washout period and returned to the laboratory, where they were randomized to receive
      intranasal treatment with either CO2 or no treatment. Thirty minutes after treatment,
      subjects underwent a nasal challenge with allergen. Seven subjects were challenged with
      ragweed and five subjects were challenged with grass. Subjects had another 2-weeks washout
      period and were then crossed over to the other treatment followed by a similar challenge.
      Previous work in our laboratory using a similar challenge system showed that allergen-induced
      inflammatory changes are back to baseline 2 weeks after the challenge.

      Subjects: Twelve subjects participated. Subjects were studied outside their allergy season.
      All subjects were healthy except for mild asthma requiring only as-needed bronchodilators.
      They were not on any medications and had not received antihistamines or leukotriene receptor
      antagonists for at least 1 week and intranasal steroids for at least 1 month before
      enrollment and for the duration of the study.

      Treatment: CO2 was applied for 10 seconds in each nostril using a special applicator (plastic
      tight-seal nosepiece) attached to a CO2 canister and a flow control valve. It was delivered
      at a flow rate of 0.5 standard L/min with the mouth open to prevent inhalation. Thus, for
      20-second duration of administration, the total dose of CO2 delivered was 167 mL. The amount
      of CO2 delivered to the mucosa is unknown. The no-treatment arm involved placement of the
      device but no gas was delivered. Therefore, neither the subjects nor the investigators were
      blinded to the treatment administered. The no-treatment arm did not involve the delivery of
      air without CO2 to the nose because we were concerned that blowing dry air into the nose
      might cause a mucosal reaction that could confound the results. We have previously shown that
      cold, dry air challenges create a hyperosmolar environment, triggers mast cell activation,
      and induces a nasonasal reaction.7 Thus, because our primary outcome was the objective
      measure of the nasonasal reflex, we avoided this possibility.

      Nasal Challenge: The subjects were allowed 15 minutes to acclimatize to the laboratory
      environment before challenge. Baseline sneezes reflecting the 15 minutes of acclimatization
      and nasal and eye symptoms were recorded followed by collection of a nasal scraping for
      quantitation of eosinophils in nasal secretions. Sneezes were recorded by the subjects during
      each of the assessed intervals of the challenge protocol. The subjects were reminded to keep
      track of the number of sneezes by the research coordinator who was present for the duration
      of the challenges. Intranasal CO2 or sham was then applied for 10 seconds to each nostril.
      Thirty minutes later, sneezes and symptoms were recorded again, to reflect the 30-minute time
      period, and nasal challenge was initiated. Because we were interested in evaluating the
      effect of the treatment on allergen-induced nasal reflexes, we used filter paper disks to
      perform the challenges and monitor the secretory response as previously described.

      Briefly, 8-mm filter paper disks (Shandon, Inc., Pittsburgh, PA) were used for both nasal
      challenge and collection of resultant secretions. They were placed on the anterior nasal
      septum, beyond the mucocutaneous junction, under direct vision using a nasal speculum,
      forceps, and a headlight. Fifty microliters of challenge solutions were placed on the disks,
      which were then applied to the nasal septum for 1 minute. Thirty seconds after removal, two
      preweighed filter paper disks were placed on both sides of the nasal septum for 30 seconds,
      collecting nasal secretions from the challenge site (ipsilateral) and the contralateral
      nostril. These disks were then immediately placed back into microtubes and weighed. The
      difference in their weight before and after challenge was the weight of produced nasal
      secretions, which was recorded in milligrams. Ten minutes after each challenge, the number of
      sneezes as well as symptoms on each side were recorded by the subjects reflective of the
      10-minute interval The first challenge was performed using phenol-buffered saline, the
      diluent for the allergen extracts, and this was followed by 2 increasing doses of grass or
      ragweed allergen. The time from treatment administration to the first allergen challenge was
      approximately 40 minutes and to the second allergen challenge, 50 minutes. The amount of
      allergen applied on the paper disks for challenge were 333 and 1000 BAU (bioequivalent
      allergy unit) of grass allergen extract (Hollister-Stier, Spokane, WA) or 50 microliters of
      ragweed antigen extract at concentrations of 1:666 and 1:200 w/v (Hollister-Stier). The
      subjects came back to the laboratory 24 hours later and underwent a scraping of their nasal
      secretions to evaluate for eosinophil influx.
    

Intervention name(s): Carbon dioxide, USP; Placebo
Intervention type(s): Device; Other
Intervention description(s): Carbon dioxide (CO2) delivered via a nosepiece at a flow rate of 0.5 (± 0.05) SLPM for 10 seconds /nostril; Nasal placebo
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)