All mammals, including man, have two nasal passageways which typically carry a differing apportionment of tidal airflow [1]. Periodic change in inter-nasal airflow apportionment is known as the nasal cycle. In healthy humans, the nose is the preferred entry point for air entering the airways [2-5], serving an important role in maintaining airway health by entrapping inhaled pathogens and pollutants as well as heating and humidifying inhaled air [6,7]. During nasal breathing, the nose recovers around 30% of exhaled heat and water vapour [8] and provides a region for olfaction to occur [9]. The entire conducting airway is lined with an airway surface liquid (ASL) that not only provides the means of entrapment of inhaled pathogens, but is also the medium through which heat and water must pass though from the underlying mucosa [10].

Currently it is thought that the nasal cycle controls the balance between heat and water fluxes from the ASL [3]. Other sources believe it enables cells and glands to rest and recharge [11]. No known definitive work in the current literature analyses or confirms these ideas.

Gaining transducer access along the complete nasal cavity is not practical without altering the complex geometry or eliciting a tissue reaction. For this reason, computational modelling is a useful manner to predict conditions within the nose. While some physical and computational nasal air conditioning models have been developed [12-17], none appear to have considered the complete nasal airway or the effect of the ‘nasal cycle’ on ASL hydration levels. This works seeks to remedy this through the incorporation of airflow apportionment as a result of the nasal cycle into a computational nasal air-conditioning model, which demonstrates new insights into this physiological phenomenon. This work also introduces for the first time the variable of ASL water equivalent height (H e,asl ) which quantifies the change in ASL hydration status as a combination of the different hydration responses of its binary layers to water loss or gain.

Mucociliary clearance

The defensive mucus layer within the nose is normally transported in the posterior direction at around 3–25 mm/min by the synchronized beating of motile cilia protruding from pseudo-stratified columnar epithelium [18,19]. This propels the upper mucus layer toward the pharynx where it is cleared by swallowing or expectoration.

ASL hydration/dehydration

The nose is located at the opening of the conducting airway so its mucosa is exposed to a significantly greater air-conditioning demand than that encountered when moving toward the distal airways [12]. While many studies into maximal ASL supply have been undertaken for the trachea and bronchi [20-25], it is not possible to use those data for the nose model used in this investigation since the number of submucosal gland openings varies throughout the airway [26].

The ASL lining the entire conducting airway consists of two functional layers; the periciliary layer (PCL) overlaying the airway mucosa and the sticky mucus gel blanket facing the airway lumen. The PCL provides a platform for mucus transportation through motile cilia beating [24,27,28] while the sticky mucus layer has the important role of entrapment of inhaled pathogens/particles and the absorption of gaseous water-soluble air contaminants [20,29-31]. Recently this stratification and its implications for ASL hydration have been further clarified [32]. The gel-on-brush model recently proposed [32] describes how the mucins and mucopolysaccharides released from the mucosa become either tethered to the cilia to form a brush like structure, or alternatively, remain un-grafted and move into the mucus layer. The resultant variation in mucin density suggested by this model helps explain its stratification and, more importantly, also indicates why each ASL layer has a differing hydration behaviour. This variation is quantified in terms of osmotic bulk modulus and it serves to protect the PCL from significant height change over the normal ASL hydration range to ensure efficient mucociliary transport can be maintained [33,34]. Rehydration of the ASL follows through mucosal glandular [20] and purinergic supply channels [35]. During exhalation, supplementary rehydration also occurs as a consequence of mucosal cooling during inhalation. This enables the fully saturated, warm, exhaled air (at near core body temperature) to condense on the cooler ASL. Any excess ASL water content is reabsorbed through the airway epithelium [20]. Summarising the ASL hydration/height interplay [32]:

1. During normal ASL hydration/dehydration, water preferentially enters or leaves the mucus layer, causing it to undergo significant changes in height. The PCL layer remains at a relatively constant height of 7–10 μm, ensuring mucociliary transport is maintained. 2. Severe ASL dehydration causes high levels of water to be drawn from both mucus and PCL layers which causes significant reduction in PCL height.

During severe ASL dehydration, a reduction in PCL height causes mucociliary transport dysfunction [34,36]. Although it has not been investigated, it has been hypothesised that the likely mechanisms causing this may be mucus filling the interciliary spaces, or through the mucus layer compressing the motile cilia [32].

Nasal cycle

It is reported that a proportion of the population, ranging from 20 – 40 % [1,37,38] to over 80% [1,39-41], experience periodic vascular congestion/decongestion of the erectile tissue within either side of the nose [41,42]. One airway demonstrates enlarged turbinates, obstructing airflow, while those in the other passageway are contracted. The airway that offers less obstruction to airflow is termed ‘patent’ while the other is referred to as being ‘congested’. The ‘nasal cycle’ describes the alternating patent and congested status of each nasal airway for periods ranging from 1 to 7 hours [43]. The span of the nasal cycle is made up from combinations of discrete ultradian periods spanning 1-1½ hours [39] and usually goes unnoticed since the total nasal airflow resistance remains unchanged [9,11]. While the most apparent outcome of this cycle is that it serves to regulate the bias of air mass flow partitioning between the airways [1,44], the functional purpose of the nasal cycle is not fully understood. Currently it is thought to control the balance between heat and water fluxes from the ASL [3], as well as enable cells and glands on the congested side to rest and recharge [11], but no definitive work in the literature analyses or confirms these ideas. Mucociliary transport is also faster within the congested airway [40], however the reasons for this are currently unknown.