The evolution of humidification in CPAP therapy means OSA treatment is catching up with human respiratory needs and compliance is likely improving

Humidification of the respiratory tract has been critically important to vertebrate physiology since the first tetrapods (eg, Dipnoiformes or “lungfish”) began gulping air by buccal breathing.¹ Numerous complex physiologic mechanisms exist in order for terrestrial or air-breathing vertebrates to maintain the integrity of the respiratory apparatus and consequently survive.

Approximately 350 million years after the lungfish evolved, in 1981 to be precise, nasal CPAP, the contemporary counterpart to buccal breathing, was introduced for OSA therapy.² In addition to the bulky uncomfortable masks, the original CPAP machines were large and noisy, and lacked humidifiers. In spite of these obstacles, CPAP became, and still is, the most important and preferred therapy for OSA. It is not only the specific antidote for the imbalance between excessive negative airway pressure and inadequate upper airway dilating forces during sleep that leads to an obstructive airway, it is also noninvasive. CPAP is therefore a medical rarity, a highly effective therapy for various potentially lethal conditions that can be used without risk of any major complications.

However, there are a number of factors, such as nasal congestion and dryness of the upper airway, that preclude successful use of CPAP. In our experience, aggressive humidification of the nasal airway, which includes the use of heated humidifier systems, is fundamental to improving nasal CPAP compliance.

Basic Principles of Humidity
The amount of water vapor or humidity contained in air depends on the barometric pressure and temperature (see Figure).³ The absolute humidity is the actual or absolute amount of water vapor present in any given volume of air expressed in mg H2O/L. The maximum amount of water that can be held at a given temperature and pressure, also expressed in mg H2O/L, is the maximum capacity. Relative humidity is the ratio of the absolute humidity to the maximum capacity, expressed as a percentage. Increasing temperature increases the capacity to hold water vapor and therefore, unless absolute humidity also increases, a higher temperature decreases relative humidity and vice versa. Air is considered to be saturated or at the dew point temperature when the relative humidity is 100%, that is when the water content equals the maximum capacity. Any subsequent decrease in temperature below the dew point results in condensation. This becomes extremely important when considering the effectiveness of humidifiers and the delivery of warm moist air in a cool environment and/or through a cool tube.

Nasal Physiology
Under normal conditions, the nasal airway passages act as the primary “air conditioner,” responsible for removing particulates and warming and humidifying inhaled gases.^4-6 During exhalation, the nasal system then attempts to reclaim the heat and water vapor that had been added during inspiration. Considering the size of the human nasal airway, the velocity of airflow, and the absolute amount of heat and water exchange that occurs, the efficiency of our nasal humidifier is remarkable. In the course of passing through the nose to the back of the nasopharynx, air is warmed from ambient temperature (eg, average room temperature of 20°C) to approximately 35°C. Therefore, assuming an ambient relative humidity of 50%, the absolute humidity added by the nasal mucosa increases from 9 mg/L to 35 mg/L, providing a relative humidity of 90%. By the time that that air reaches the air-blood interface in the lungs or the alveolar gas exchanging membranes, the absolute humidity has been increased further to 44 mg/L and the relative humidity measures 100% at a temperature of 37°C, the remainder of heat and water having been added by the lower respiratory airway.

Air conditioning by the nasal mucosa is accomplished by virtue of the close apposition of highly vascular erectile sinusoid tissue (turbinates) and a slightly turbulent airflow distributed over a relatively large surface area. Periodically or every few hours, the airflow through one nasal airway decreases, presumably in order to replenish its mucosa, while the other side air conditions. Because this reverse process on exhalation is less efficient, the nasal mucosa, which is essential to the air-conditioning process, is prone to desiccation. Unless heat and humidity are replenished to the mucosa, nasal obstruction and morphologic alteration of the respiratory lining develop. Consequently, the primary nasal functions of humidification and removal of airborne particulates become much less efficient. In addition to medications, anatomic abnormalities, various disease states, and physiologic factors, such as being in the supine position, reduce the ability of the nose to condition cold dry air.⁷

Positive Airway Pressure Effects
Therapy with positive airway pressure breathing can adversely affect nasal airway function and effectiveness of nasal CPAP.^8,9 Research has shown that inadequate humidification can cause respiratory mucociliary dysfunction, nasal mucosal inflammation, increased nasal mucosal blood flow, increased nasal congestion, and decreased static pulmonary compliance.^8-12 Although adverse effects of inadequate humidification may be at least partially reversible, they are directly proportional to the duration of the exposure and the properties of the gas.⁸ Warmer drier air has an enhanced ability to extract moisture and dry the upper airways. Studies have also shown that delivering air with a relative humidity of 40% at 40°C leads to more mucociliary dysfunction than similarly saturated air at 34°C.

Inhalation of cool dry air increases nasal congestion and causes release of inflammatory mediators.^10,11 This phenomenon probably accounts for patient reports such as “Doctor, I must have gotten a cold in the sleep lab after using CPAP because my nose was runny all day afterwards.” Due to the vascular reactivity of the turbinates and nasal congestion, nasal airway resistance increases. The patient may complain of claustrophobia or of receiving inadequate airflow through the nose, thereby promoting mouth breathing or causing the unconscious removal of the CPAP mask during sleep. Mouth breathing also may increase pharyngeal obstruction due to relaxation of the mandibular muscles, increase unidirectional high airflow through the nose and mouth, further dry the respiratory lining, and even affect the operation of the CPAP equipment.

Another issue with increased nasal airway resistance is that it results in a greater pressure drop between the mask and the pharynx where there is a critical positive pressure necessary to maintain airway patency. In addition to the severity of sleep apnea, research has shown that baseline nasal resistance is a predictor of initial CPAP acceptance.¹³ While increased nasal resistance is not predictive of sleep disordered breathing per se, increased nasal resistance can predispose to oral breathing that leads to drying of the respiratory mucosa and increased work of breathing. Keep in mind that the patients’ perception of nasal congestion may not correlate with actual resistance to airflow.¹⁵

For all of these reasons, physicians may prescribe higher CPAP mask pressures than necessary, which further reduces a skeptical patient’s comfort with an already awkward therapy. It is quite clear that avoidance of delivery of excessive pressures or improperly humidified air is critically important to patient comfort and therefore successful CPAP therapy.

CPAP Humidifier Systems
Humidification through CPAP systems has been traditionally delivered in one of two ways. Cold pass-over humidifiers deliver water vapor by having the air flow over a reservoir of cool water. This technique is inefficient and is limited by evaporative cooling of the water reservoir. Heated pass-over humidifiers are more efficient due to increased rate of evaporation and can deliver substantially greater amounts of water vapor and decrease water loss during respiration as compared to cold pass-over humidifiers.^15-17 Generally speaking, effectiveness of humidification varies inversely with the rate of airflow.^16,18 Some theorize that higher airflows lead to more air escaping exhaust ports rather than being respired and therefore less efficient humidification; however, the differences in humidification between commonly used CPAP pressure settings are modest at best.¹⁶

The increased absolute humidity delivered by heated pass-over humidifiers may be limited by water vapor condensing in the CPAP tubing. This phenomenon becomes an issue when the warm humid air leaving the humidifier falls below the dew point while it is being transported through relatively cool tubing, especially as the ambient room temperature is decreased. Condensation that forms in the tubing can cause inconsistent pressures when measured at the mask.¹⁹ One recent technological advance is a CPAP device that employs both a heated passover humidifier along with a heated connecting tube from the humidifier to the mask that helps prevent this fall in air temperature and the accompanying condensation. Nilius et al demonstrated that with an ambient room temperature of 14°C, overnight condensation in the tubing can be decreased from approximately 35 mL to 2 mL.²⁰ These changes were also associated with improved sleep and decreased symptom scores.

The optimal level of humidification has not been clearly delineated; however, we do know that an absolute humidity of 30 mg/L appears to attenuate increases in nasal airway resistance associated with simulated mouth leaks.²¹ Research also has demonstrated that increased nasal mucosal blood flow from simulated mouth leaks can be attenuated with inspired air warmed to 29°C and a relative humidity of 70%.¹² Furthermore, it appears as if mucosal drying plays more of a role in increasing nasal airway resistance than does mucosal cooling.²¹ Therefore, delivery of air to the nose with an absolute humidity of around 30 mg/L and a relative humidity of around 80% to 90% at a temperature of around 30°C may be best.

Although heated humidification can increase the water vapor content, mouth or mask leaks increase unidirectional flow and can overwhelm the capacity of a heated humidifier.²² Aside from using a heated humidifier, research has shown that full-face or nasal-oral CPAP masks attenuate the loss of humidity that is associated with mask leaks.²² Consequently, the respiratory mucosa can reclaim moisture from saturated expiratory gas and minimize water loss. Despite improved nasal symptoms with full-face as compared to nasal CPAP masks, comfort and compliance are better with the nasal CPAP masks and patients generally prefer the smaller nasal masks.^22,23

Complications and Adverse Affects
Aside from the hassle associated with wearing a bulky mask, “rain-out” or condensation forming within the mask and/or tubing that drips on the patient’s face is particularly bothersome. Other concerns include the risk of infection, especially given reports of microbes contaminating ventilator tubing, humidifiers, and nebulizers. Manufacturers have eliminated older “bubble-through humidifiers” because of the fear that aerosolized water particles could transport bacteria and increase the risk of respiratory tract infection. However, a more recent study has demonstrated that heated convection humidifiers, as used in current CPAP systems, do not aerosolize water droplets.²⁴ Instead these systems produce molecular water vapor, which cannot transport bacteria or other microorganisms. Therefore, it is unnecessary to use sterile water to prevent infections. Using distilled water, however, is still a good idea since minerals found in tap water may degrade the operation of the heating element.

Clinical Experience
Researchers have assessed clinical efficacy for the use of humidification in combination with nasal CPAP in three different outcomes: controlling nasal/upper respiratory symptoms, utility during initial CPAP titration, and long-term benefits/compliance. They have found that up to 65% of patients using CPAP therapy complain of upper airway dryness, nasal congestion, nosebleeds, or sore throat that limits the use of therapy.^25,26 At present, possible therapies include avoidance of drying medications, nasal corticosteroids, nasal moisturizing solutions, full-face masks, and humidifiers (cold or heated). Wiest et al compared heated humidification to oily nose drops for the treatment of CPAP-related upper airway dryness. Heated humidification not only proved to be superior in controlling the troublesome symptoms, but all 12 patients in the humidification group reported decreased dryness and improved comfort.²⁷ In fact, all patients intending to discontinue CPAP therapy because of upper airway dryness continued therapy when humidification was added. It should be noted that the use of oil-based nasal drops increases one’s risk of developing lipoid pneumonia, and, therefore, this option should be avoided in any case. Rakotonanahary et al showed that upper airway symptoms developed in 56% of CPAP users.²⁸ Of those with symptoms, 50% improved with use of a cold pass-over humidifier and 87% of the remaining patients improved with a heated humidifier.

Several studies have looked at the addition of heated humidification during initial CPAP titration use and its effect on upper airway dryness, CPAP compliance, and patient comfort in the short term without finding significant benefit to humidification.^26,29,30 However, it is quite possible that the long-term inflammatory and local irritant effects of dry air on the respiratory mucosa cannot be appreciated in the short trial periods in these studies.

There are numerous confounding factors that will determine long-term compliance with nasal CPAP, and, therefore, it is difficult to identify the independent effect of heated humidification. There are also no long-term studies that have examined the compliance using newer humidification devices that maintain optimal humidification by means of a heated tube without the complication of condensation. Using older technology, several studies have shown that heated humidification increased long-term compliance. Massie et al31 looked at CPAP naive patients in a crossover design study and compared heated humidification, cold pass-over humidification, and no humidification for a total of 8 weeks. Compliance improved with heated humidification as compared to no humidification, but the effect was modest, approximately 0.59 hours improvement per night. On the other hand, study participants with heated humidification felt more refreshed upon awakening and preferred the heated humidification as compared to the cold pass-over humidifier. Interestingly, preexisting nasal symptoms did not predict humidifier choice. Rakotonanahary et al28 also demonstrated an improvement in compliance by 1.87 hours with heated humidification as compared to dry air in those with upper-airway symptoms. Mador et al32 looked at patients during their first year of therapy using CPAP and demonstrated improvements in upper airway symptoms when heated humidification was used as compared to dry air; however, patient compliance was not improved with the intervention.

Previous limitations to existing studies include poorly monitored and delivered humidification. While there were protocols in place for patients to adjust their level of humidification, ambient room temperature and resultant condensation were not recorded routinely. It would be important to see a larger randomized study looking at long-term compliance and efficacy in patients with CPAP using a heated humidifier with a heated delivery tube where the actual delivered humidification and condensation were measured and recorded.

Conclusion
The nasal airway is essential for proper conditioning of air with heat and humidity before entering the lungs. The nose also has an efficient mechanism for recapturing water vapor during expiration. However, breathing cold dry air with nasal CPAP can alter the structure and function of the nasal mucosa, thereby overwhelming these mechanisms. Patients can experience many upper airway symptoms, and successful long-term therapy with nasal CPAP might be unnecessarily jeopardized. Studies have shown that heated humidification reduces these adverse effects and improves patient comfort. Some studies have demonstrated improved compliance, but more research is needed to assess the long-term effects, especially using newer nasal CPAP systems that provide more optimal heat and humidification.

While some of our patients elect not to use these devices, we prefer to preempt nasal problems since the incremental cost of adding humidification to CPAP treatment is minimal and long-term CPAP treatment compliance is generally dictated by the patient’s response to therapy within the first 3 months.³³ In our area—the Intermountain West—physicians routinely provide heated humidifiers to all patients prescribed nasal CPAP. The use of humidifiers in other geographic areas may need to be determined according to local conditions and standards of practice.

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Mark A. Rasmus, MD, is a pulmonary, critical care, and sleep medicine fellow at the University of Utah and LDS Hospital in Salt Lake City. In September he will join Idaho Pulmonary Associates in Boise. Robert J. Farney, MD, DABSM, is director of the Intermountain Sleep Disorders Center, a member of the pulmonary division at LDS Hospital, and an adjunct professor of medicine at the University of Utah College of Medicine, all in Salt Lake City.