Air Cleaners for Children and Adolescents With Asthma and Dog Allergy
Condition: Asthma; Allergy
MeSH terms: Asthma; Hypersensitivity
Study type: Interventional

Summary: 
      The purpose is to find out if Icleen IQAir, HEPA-filter air cleaners with high capacity and
      pre-set speed functions, have a beneficial effect on patients with asthma and allergy to
      dogs.

      Air cleaners will be installed in the bedrooms and living rooms in the homes of children and
      adolescents aged 8-17 years at the study entry, with allergy to dogs, but not to house dust
      mites.

      The investigators will look upon the significance of this study, and of a previous study with
      a similar design and the same main parameters to find out if this trial supports the results
      of the first trial by the same project leader, or makes it likely that the seemingly
      beneficial effects of the first study occurred by chance.

      Main parameters:

        -  hyperventilation cold air challenge test

      Supportive parameters:

        -  serum ECP

        -  symptom scores

      The trial will be a parallel, double blind placebo controlled one.
    

Detailed description: 
      Project leader: Leif Bjarte Rolfsjord, M.D., section leader, Paediatric Department Sykehuset
      Innlandet HF Elverum-Hamar; Ragnhild Halvorsen, M.D. Ph.D., Voksentoppen, Paediatric Clinic,
      Rikshospitalet; Leiv Sandvik, Ph.D. professor, research leader statistics, Competence Centre
      for Clinical Research, Ullevaal University Hospital

      AIM:

      To examine if powerful air cleaners with HEPA-filters and a pre-set speed function making it
      possible to run the air cleaners at a high, but noisy speed at acceptable times, and , if
      wanted, at a lower, but less noisy speed at other times, (Icleen IQAir®) , have a favourable
      effect on asthma in children and adolescents aged 8-17 years, who are allergic to dogs, but
      not to house dust mite. To look at this study separately, but also look upon the total
      results of this study and a previous study performed by the project leader.

      BACKGROUND:

      The first study is not yet published. We found signs of clinically significant effects of
      active air cleaners by the parameters ECP in serum and bronchial hyperreactivity by a cold
      air hyperventilation test, but the results gave p-values at the border of statistical
      significance, p=0.104 for FEV1 reduction, and significant results, p=0.018 for differences in
      the change of ECP. The number of patients included in the study was 49, a lower number than
      wanted in the first place. We did not find significant effects on Liz Juniper's Life Quality
      Scale scores. Yet, there are reasons to believe that the results of the first study may have
      clinical significance. A cold air hyperventilation test reflects a real life situation in
      interior parts of Norway, resembling outdoor winter conditions strongly. In the first study
      Allergy Control encasing over pillows, eiderdowns and mattresses were applied compared to
      placebo, but no signs of effects were found on these children aged 7 to 17 with allergy to
      dog or cat, but not to house dust mites. The reason to exclude house dust mite allergic
      patients in the first trial was to examine if encasings could have any effect on patients
      without house dust mite allergy, and the fact that house dust mite allergy is less common in
      Northern interior areas, where the trial took place. Other studies indicate, however, that
      air cleaners can reduce allergens from dogs and cats, but not most other indoor allergens
      (3). We want to perform a new trial, and publish the results from each trial in one
      publication, but also look upon the results of a meta-analysis of both studies. Our hope is
      that the two trials can give more reliable information about the effects of the air cleaners.
      This time, no dust analyses will be taken, because dust analyses from the first trial, sent
      to dr. Susanne Lau at the Charité-Virchow Clinic in Berlin, showed that the air cleaners
      removed considerable amounts of dust (personal message from dr. Lau). The results have been
      summarised in an article by Groth C et al. in Allergy in 2002, and a manuscript for an
      article is now sent to Allergy for publication. The efficiency of IQAir air cleaners has also
      been documented by Stiftung Warentest in Germany. Due to limited resources and the signs of
      low sensitivity in such a trial, Liz Juniper's Life Quality Scale will not be applied this
      time. For economic reasons, hair samples for nicotine analysis will not be taken this time.

      Since the first trial was completed, an important improvement of the air cleaners has arisen.
      A new panel makes it possible to pre-set the air cleaners at different speeds or on and off
      at different times of the day, at different days of the week. Once a day, the speed can be
      changed to another speed or turned off, and once a day, it can be turned back to the original
      speed in advance. In addition, the pre-set function can be overridden manually at any time.
      In the first trial, the timer on and off function could turn the air cleaners off once a day
      and on once a day, with no active cleaning during the timer off intervals, and no weekday
      differentiation of the timer. This improvement increases the likelihood that the air cleaners
      will be used at higher (and more noisy) speeds at times when nobody is at home, resulting in
      lower levels of flying allergen dust levels even at times when people are at home.

      In the first trial, we did not find significantly stronger effects in homes with animals than
      in homes without animals. Only a fourth of the homes had animals through the whole trial
      period. For this reason, we will only include homes without pets this time, in order to get a
      more homogenous population. In the first trial, we had a lower age limit of 7. This time, the
      lower age limit is 8, to make it easier for patients to co-operate, avoiding frustration for
      seven-year-olds who may be excluded due to co-operation difficulties. The reason that we
      require dog allergy this time, not dog or cat allergy as in the first trial, is that one
      trial indicates that air cleaners only reduce the amount of airborne cat allergens marginally
      if no cat is in the room. This trial was performed in homes with cats (5). On the other hand,
      a trial of effects of air cleaners in homes with dogs showed a significant reduction of dog
      allergens even in rooms where dogs were not present (1). The studies are difficult to
      compare, however, because different dust sampling methods were applied.

      MATERIAL:

      30 patients from Hedmark county in south-eastern Norway will be examined for the study at the
      start. The patients will be selected from journals of patients having visited the hospital
      for asthma during the previous three years, having had verified allergy against dog, but not
      house dust mite.

      TRIAL DESIGN:

        1. Active group: IQAir® air cleaners, one in the patient's bedroom, and one in the room
           mostly used by the patient outside the bedroom; with real pre- and main filters.

        2. Placebo group: As above, but the main filter substituted by a placebo filter. If the
           parents of the child do not live together, and the child visits the other parent at
           least every second weekend, both parents will be supplied with air cleaners of the same
           type, with equivalent placing of the cleaners.

      The air cleaners are labelled either A or B, indicating if they are real or fake. Until
      closing of the trial, only the manufacturer will know the code. The patients will be
      randomised either to A or B, with no stratification. The air cleaners are sealed. Hence, it
      is not possible to open them to see what kind of filters they have, without breaking the
      seal. Even the placebo filters will seem real, for people not accustomed to looking inside
      air cleaners.

      Protocol attachments:

      Skin prick tests and specific IgE will only be performed at visit 1. Other examinations and
      questions applied at both visits.

      ATTACHMENT 1: Clinical examination

      Height, weight, inspection of thorax, any stridor must be recorded, respiration frequency,
      lung auscultation. The signs recorded after the Kjell Aas scale from P0 to P6:

      P0: Normal. P1: No discomfort. Slightly weakened auscultatory ventilation sound. P2: No
      discomfort. A few sibili (fine wheezing sounds) or rhonchi at auscultation. Prolonged audible
      expirium. No retractions.

      P3: No discomfort at rest. Abundant obstructive sounds. Slight jugular retraction, some use
      of auxiliary ventilation muscles. Possibly elevated shoulders.

      P4: Some discomfort at rest. Abundant obstructive sounds. Fine wheezing heard without
      stethoscope. Jugular/intercostal retractions. Use of auxiliary ventilation muscles. Worse
      (P5) after cough.

      P5: Considerable discomfort at rest. Abundant obstructive sounds. Wheezing expiration.
      Wheezing without stethoscope. Energetic use of auxiliary ventilation muscles. Possibly slight
      cyanosis.

      P6: Alarming obstruction. Often even inspiratory obstruction. NB! Weak respiratory sounds,
      but retractions and use of auxiliary muscles and tachypnoea are especially alarming. Possible
      cyanosis.

      ATTACHMENT 2: Cold air provocation test - method Material

        1. Rhes-pro® cold air unit delivering cold air, with a 5.2% CO2 content, to avoid
           hypocapnia at hyperventilation. The apparatus must be calibrated to give a standardised
           temperature, -15C of the inhaled air at lip level, and 5.2% CO2.

        2. Flow volume spirometer with computer.

        3. Before the test, one must make sure that there is enough air and CO2 for the unit.

      Medication

      Drugs that can affect the results must be avoided at a certain interval. In our study, the
      following drugs are withheld at the indicated intervals before the test:

        -  Short acting beta-2-agonist: 12 hours

        -  Long acting beta-2-agonist: 24 hours.

        -  Beta-2-agonist slow release oral drugs: Generally not used in our clinic. If yet taken :
           3 days

        -  Theophylline slow release oral drugs: Generally not used in our clinic. If yet taken: 3
           days

        -  Antihistamines: 7 days

        -  Leukotriene antagonists: 48 hours.

        -  Atropine derivatives (ipratropium bromide): 8 hours. After the test, the patient can be
           given the rest of his ordinary morning drugs.

      Time of the day

        1. The test should be performed at the same time every time, preferably in the morning.

        2. The patient should rest for 15 minutes before the test, to avoid influence by physical
           exercise (bicycling, running up stairs etc.).

      Test method

        1. Tests performed on Mondays must be avoided to prevent influence by casual contacts and
           activities in the course of the weekend before the test.

        2. Travels including staying overnight away from the home for more than a week should be
           registered, and the test should be performed more than one week after arriving home from
           holiday.

        3. The patient must have normal clinical signs (P0) before the cold air provocation, or the
           test must be postponed.

        4. Take flow volume test, best FEV1 out of 3 attempts. A printout of the best spirometry
           attempt must be stored in the research archive. The flow volume tests shall be performed
           in a sitting position. The patient must use a nose clip during spirometry and cold air
           provocation.

        5. Provided FEV1 is >70% of predicted, the test is started. If <70%, it is postponed.

        6. The air mixture flow is calculated by the pre-provocation best FEV1 value, by
           multiplying FEV1 by 20 for children less than 13 years of age at the first visit, and by
           26 for the adolescents more than 13 years of age at the first visit. The patient remains
           sitting during the cold air provocation.

        7. The patient is instructed to breathe rapidly and deeply through the mouthpiece during
           the provocation, which lasts for 4 minutes. In practice, the test is performed by
           letting the child breathe sufficiently to keep a connected balloon or ventilation bag
           halfway filled.

        8. Spirometry with FEV1 must be performed straight before and 2 minutes after provocation.

        9. MEF50 (=FEF50) at each spirometry being recorded as the spirometry giving the best FEV1
           will be registered.

       10. Auscultation signs immediately before each series of three spirometry attempts, and
           possible cough, will be registered.

       11. After the post-provocation spirometry (two minutes after the provocation), salbutamol,
           Ventolin 0,1mg meter dose inhaler by Volumatic will be given for reversibility test; 2
           puffs for patients weighing less than 45 kg, and 4 puffs for patients weighing 45 kg and
           more; one puff at a time; 5 inhalations per puff. New spirometry will be performed 5
           minutes after giving Ventolin, and FEV1 is registered again, in absolute value, and
           percentage of the first value, before cold air provocation.

       12. Even if the risk for acute severe asthmatic symptoms is low, a nebuliser for giving
           salbutamol and adrenaline for subcutaneous injection and equipment for intravenous
           administration of antiasthmatic drugs will be easily available.(The treatment scheme
           from the Norwegian Paediatric Association's acute therapy book will be applied.)
           Evaluation of the test results Percentage fall in FEV1 and FEF50 will be applied as a
           parameter of bronchial reactivity. More than 10% fall in FEV1 after cold air or more
           than 10% rise in FEV1 after inhalation of Ventolin, is considered significant.

      Printouts of the spirometry results will be saved. Patient registration sheet cold air
      hyperventilation test (Printouts from spirometry to be attached).

      The following data will be noted:

      Time of day, hours, minute. Height (cm) Weight (kg) Assisted by (nurse) Assisted by (doctor).

      Questions to be asked:

      Staying away from home for more than 2 weeks last month or during trial? Staying overnight
      away from home last week? Staying overnight for more than a week, less than one week ago?
      Inhaled drugs - Ventolin, Serevent, Flutide, doses, numbers of hours ago. Other drugs, route
      Dose x times a day Last dose, number of hours ago

      To be recorded from spirometry:

      Best FEV1 (pre-test) litres per minute Temperature at mouthpiece: (will be held at -15 °C).
      Air flow in cold unit (litres per minute) CO2 flow in cold unit (litres per minute) Number of
      minutes of provocation Number of pauses Patient's performance will be recorded as good,
      acceptable or unacceptable.

      The following values and signs noted before provocation, 2 minutes after provocation and 5
      minutes after Ventolin given in a spacer (Volumatic®).

      FEV1, FEV1 % increase (+) or decrease (-) of pre-test MEF50 MEF50 % of first Aas score
      (P0-P6) Cough Other signs or symptoms If other rescue medication is given than Ventolin in
      Volumatic, it must be noted.

      ATTACHMENT 3: Inquiry about animal contact.

        1. Are there pets in the home?

        2. Did you react by nose symptoms, sneezing, cough or breathing difficulties the last time
           you were close to a dog without having taken drugs against asthma or allergy?

        3. What kind of pet do you have in the home:

           If animal removed the last half year, how many months ago? Animal now? Number of
           animals? Specify if you have cat, dog, rabbit, hamster, other furred pets, budgerigar,
           other birds, fish, other animals

        4. Are you (patient) in contact with animals outside the home? How often; what kind of
           animal? ATTACHMENT 4: Inquiry about smoking. The staff fill in questions to patient if
           the patient, or anybody else in the home smokes, and if smoking in the home totals less
           than 10, 10-20, or more than 20 cigarettes a day.

      ATTACHMENT 5: Questions about fitted carpets, humidity, vacuum cleaners, mechanical
      ventilation systems.

      The following questions are asked by staff to parent or accompanying person (what person will
      be recorded).Filled in together with:

        1. Do you have fitted carpets?

        2. Do you have fitted carpets in the child's bedroom?

        3. Do you have fitted carpets in the living room?

        4. Do you have fitted carpets in other rooms?

        5. Do you think that you have more than 5 cm of dew or frost on the inside of the window of
           the child's bedroom?

        6. Is there any smell of mould in your house?

        7. Where in the house is there a smell of mould?

        8. Can you see mould or rotten patches in any room?

        9. If yes, where can you see it?

       10. What kind of vacuum cleaner do you have?

       11. Is there, except for ventilation over the kitchen stove, any kind of mechanical
           ventilation or air filtration in the home? ATTACHMENT 6: Symptom score The patients are
           asked to draw a circle around one of the numbers, from 1 through 5, indicating the
           degree of symptoms, 1 meaning no or never, 5 meaning many times each night, severe,
           always, cannot breathe through my nose or cannot breathe through my nose while sitting
           still, respectively. For patients taking antihistamines, the nose symptoms are valid for
           the last 5 days. Otherwise, the questions are applicable to the last month.

      Questions to patients at Visit 1 Sep./Oct.-05:

        1. Do you wake up at night due to asthma?

        2. How is your asthma during daytime?

        3. Do you feel your asthma when you run?

        4. Is your nose stuffy at night? To patients who have taken antihistaminic agents regularly
           for the last month this question will be asked instead: Has your nose been stuffy in
           daytime for the last 5 days?

        5. Is your nose stuffy during daytime? To patients who have taken antihistaminic agents
           regularly for the last month this question will be asked instead: Has your nose been
           stuffy in daytime for the last 5 days? Finally, a question is asked about strong asthma
           attacks last 3 months. Options for answers ar no, once or several times.

      ATTACHMENT 7: Medication. Prophylactic medication will be kept constant during the trial.
      Doubling doses of inhaled steroids for maximum two weeks during exacerbations or airway
      infections, or, in patients not taking inhaled steroids daily, taking inhaled steroids for
      maximum two weeks during exacerbations or airway infections, will be accepted. Systemic
      corticosteroids in the trial period will lead to exclusion.

      Ongoing medication: See section about cold air challenge (attachment 2)

      Pre-trial medication:

      Date prescribed or "1-3" (between 1 and 3 months ago) or ">3" (more than 3 months ago) Drug
      name Total amount of doses prescribed Generic name Drug type (tablets, oral mixture,
      injection liquid etc.) Administration route Amount per dose Measured as (ml, mg etc.) Times a
      day in good periods Times a day in bad periods or prodromal stages Max. duration of increased
      dose in days Date taken away

      Medication prescribed in trial period:

      Date prescribed Prescribed by Drug name Total amount of doses prescribed Generic name Drug
      type(tablets, oral mixture, injection liquid etc.) Administration route Amount per dose
      Measured as (ml, mg etc.) Times a day in good periods Times a day in bad periods or prodromal
      stages Max. Duration of increased dose in days Date taken away ATTACHMENT 8: Skin prick tests
      The skin prick tests are performed with a lancet with a one mm tip (ALK). All the tests will
      be performed in duplicate according to the EAACI Position paper i.e. the tests will be placed
      in a mirror fashion on the volar aspect of the forearm. The reactions will be read after 15
      minutes. The weals are to be circumscribed by a fine filter pen or ballpoint pen on the red
      skin around the weal, near the weal edge. A transparent tape strip is to be pressed over the
      circumscription and transferred over to the registration sheet. The weal size is to be
      recorded by assessment of the average weal diameter. Weals with an average diameter >3 mm
      will be considered positive.

      Skin prick test protocol - allergen extract solutions and reference solutions Skin prick
      tests shall be performed at the inclusion of the patients at visit 1, Sep./Oct.-05.
      Soluprick® extract solutions from ALK will be applied.

      Specifications:

        1. Birch: Soluprick® SQ "ALK Abello" (108) Silver birch 10 HEP

        2. Timothy: Soluprick® SQ "ALK Abello" (225) Timothy grass 10 HEP

        3. Mugwort: Soluprick® SQ "ALK Abello" (312) Mugwort 10 HEP

        4. House dust mite: Soluprick® SQ "ALK Abello" (504) D. Farinae 10 HEP

        5. House dust mite: Soluprick® SQ "ALK Abello" (503) D. Pteronyssin. 10 HEP

        6. Mould: Soluprick® SQ "ALK Abello" (417) Cladosporium herbarum 1:20 w/v

        7. Mould: Soluprick® SQ "ALK Abello" (402) Alternaria alternata 1:20 w/v

        8. Dog: Soluprick® SQ "ALK Abello" (553) Dog hair 10 HEP

        9. Cat: Soluprick® SQ "ALK Abello" (555) Cat hair 10 HEP

       10. Horse: Soluprick® SQ "ALK Abello" (552) Horse hair 10 HEP Soluprick® "ALK Abello"
           Negative Control will be used as negative control, and Soluprick® "ALK Abello" Positive
           Control, histamine dihydrochloride 10 mg/ml (ALK) as positive control.

      ATTACHMENT 9 - SPECIFIC IGE A blood sample is to be taken at visit 1 in Sep/Oct.-05, for
      specific IgE for the same allergens as the skin prick tests, except for D.pteronyssinus.
      Reagents from Pharmacia Diagnostics will be applied, and their procedures for blood sampling
      and analyses will be applied. EMLA "Astra-Zeneca" cream can be used if wanted as a topic
      anaesthetic agent before blood sampling.

      ATTACHMENT 10 - serum ECP At both visits, blood samples will be taken for serum ECP. Reagents
      from Pharmacia Diagnostics will be used, and their manuals for blood sampling and analyses
      applied.
    

Intervention name(s): IQAir Allergen 100 Air cleaners
Intervention type(s): Device
Intervention description(s): Two air cleaners are installed in the patient's room, one in his bedroom, and one in the living room. The cleaners can be run at 5 different speeds: Speed 1 filtrates 60m3 of air per hour, speed 2 filtrates 90 m3 per hour, speed 3 filtrates 130 m3 per hour, speed 4 filtrates 240 m3 per hour, and speed 5 filtrates 380 m3 per hour. A timer-on period can be pre-set for every day of the week, but the cleaner can be run even in the timer-off period, at a speed pre-set and different from the timer-on period. Different timer-on off periods cannot be selected for different days, but the different days of the week can be pre-set to apply timer-on periods or not.
Other intervention name(s): Health Pro
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Dog allergy; Pet allergy; Air cleaners; HEPA filters; Air filtration; Can f1; Asthma; Children; Adolescents; Indoor environment; Indoor allergy; Perennial allergy