Heated Humidified Continuous Positive Airway Pressure and Nasal Physiology
Condition: Obstructive Sleep Apnea Syndrome; Nasal Obstruction
MeSH terms: Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Nasal Obstruction
Study type: Observational

Summary: 
      Nasal continuous positive airway pressure can cause nasal side effects which can compromise
      compliance to therapy. Humidifiers can attenuate this effect. However, the mechanism by which
      humidified CPAP alleviates nasal symptoms has never been assessed objectively in OSA
      patients. Therefore, the purpose of this study is to examine the effect of humidified CPAP on
      nasal airway physiology with combined measurements of nasal resistance and level of
      inflammatory markers. The investigators' hypothesis is that the addition of heated
      humidification in CPAP decreases nasal airway resistance and nasal mucosal inflammation
      markers and thus, ameliorates nasal symptoms of OSAS patients.
    

Detailed description: 
      Introduction-Rationale:

      Nasal continuous positive airway pressure (CPAP) is considered to be the "gold standard" of
      obstructive sleep apnoea (OSA) treatment [1]. The most common side effects are nasal
      congestion, stuffiness or dryness and rhinorrhea which have been reported in up to 68% of
      patients responding to a questionnaire about nasal CPAP. In many of them, CPAP compliance is
      accordingly compromised.

      The mechanisms by which CPAP provokes nasal symptoms have been thoroughly studied only in
      healthy volunteers and a rodent model. Indeed, Richards et al demonstrated that mouth leaks
      causing high unidirectional nasal airflow increased nasal airway resistance and this response
      could be largely prevented by heated humidification of the inspired air. Similarly, Togias et
      al showed an elevated release of inflammatory mediators (histamine, prostaglandin D2, kinins)
      in nasal wash fluids when compressed cold and dry air was delivered through the nose. This
      effect was also prevented when warm and moist air was delivered. More recently, Almendros et
      al provided evidence that CPAP use in rats triggered early nasal inflammation.

      Of the variety of methods used to treat nasal symptoms during CPAP treatment, the most common
      is humidification of the inspired air. However, the mechanism Oby which humidified CPAP
      attenuates nasal symptoms has never been assessed objectively in OSA patients. Therefore, the
      purpose of this study is to examine the effect of humidified CPAP on nasal airway physiology
      with combined measurements of nasal resistance and level of inflammatory markers. Our
      hypothesis is that the addition of heated humidification in CPAP decreases nasal airway
      resistance and nasal mucosal inflammation markers and thus, ameliorates nasal symptoms of
      OSAS patients.

      Study design:

      BASELINE: 1. NASAL SYMPTOMS 2. NASAL RESISTANCE 3. NASAL WASH (IL-6, IL-8, TNF-a, IL-10)

      3 weeks humidified CPAP --------------> 3 weeks non-humidified CPAP <--------------

      AFTER TREATMENT: 1. NASAL SYMPTOMS 2. NASAL RESISTANCE 3. NASAL WASH (IL-6, IL-8, TNF-a,
      IL-10)

      Methods:

        1. Nasal symptoms will be assessed using a five point Nasal Score. Each of the five
           principal nasal symptoms of rhinorrhoea, post-nasal drip, sneezing, impaired sense of
           smell and nasal blockage will be binary coded as present/increased over baseline (1) or
           absent/not (0) and summed to yield a total Nasal Score between zero and five.

        2. Nasal resistance will be assessed by active anterior and posterior rhinomanometry in
           both seated and supine (for 10 min) positions.

        3. Nasal wash will be performed using a technique adapted by Hurst et al. Briefly, a
           12-French Foley catheter (Bard, Crawley, UK), modified by removal of the tip distal to
           the balloon, was inserted into the nostril and inflated with sufficient air to form a
           comfortable seal (typically 7-10ml). With the patients head flexed 45o forward, 7ml of
           warmed 0.9% saline will be instilled through the catheter and washed in and out of the
           nasal cavity three times. A portion of the pooled wash from both nostrils will be
           centrifuged to yield a supernatant for analysis of inflammatory cytokines.

      By this protocol, the following are expected: a) the reason for potential congestion and
      inflammatory response is cold and dry air passing through the nostrils (mechanical irritation
      cannot be the reason, as the pressure is equivalent in both sessions), and b) heated and
      humidified CPAP prevents (and not treats) nasal congestion.
    

Observational model: Case-Crossover
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Subjects who refer to the Center of Sleep Disorders of "Evangelismos" General Hospital of
        Athens for suspected sleep disordered breathing.
      
Biospecimen description: 
      Nasal wash will be performed using a technique adapted by Hurst et al. Briefly, a 12-French
      Foley catheter (Bard, Crawley, UK), modified by removal of the tip distal to the balloon, was
      inserted into the nostril and inflated with sufficient air to form a comfortable seal
      (typically 7-10ml). With the patients head flexed 45o forward, 7ml of warmed 0.9% saline will
      be instilled through the catheter and washed in and out of the nasal cavity three times. A
      portion of the pooled wash from both nostrils will be centrifuged to yield a supernatant for
      analysis of inflammatory cytokines (IL-6, IL-8, TNF-a, IL-10).