## 2 Cough Mechanism and Related Factors Influencing CPF  
European Respiratory Society guidelines show that coughing is a three-phase expulsive motor act constituted by an inspiratory effort (inspiratory phase), followed by a forced expiratory effort against a closed glottis (compressive phase) and then by opening of the glottis and rapid expiratory airflow (expulsive phase) [9; 10]. In addition, there is also the concept of a four-phase cough, including the irritation phase, in which a cough reflex begins with the stimulation of an irritant receptor [11]. Figure 1 shows the four phases of a normal cough.  
The inhalation cough challenge permits measurement of the sensitivity of the cough reflex during the irritation phase (Figure 1a) [9]. In general, inhalation cough challenge testing uses capsaicin [12], citric, and tartaric acid [13; 14]. A recent study developed a testing device that can easily and simultaneously measure the CPF and the time interval from the inhalation of an ultrasound-nebulized solution of tartaric acid to the cough reflex to facilitate the evaluation of cough strength and cough reflex sensitivity [3]. This study also reported that both the CPF and the time until the cough reflex was significantly lower in patients with dysphagia than in normal subjects [3]; however, further investigations are needed to clarify the relevance of these differences.  
In the inspiration phase (Figure 1b), the cough centre generates a reflex stimulation of the respiratory muscles to induce deep inspiration. Thus, the volume inspired before coughing (operating volume) and the function of the inspiratory muscles are essential for coughing [15]. The functional residual capacity is a strong and significant predictor of the operating volume (adjusted \(R^{2}=0.45\), \(p<0.01\)) [16]. In normal adults, the operating volume is approximately 3.4 L [16]. In addition, the operating volume is an important determinant of the CPF [16; 17], and the CPF has a significant positive association with the maximal inspiratory pressure, which is a marker of inspiratory muscle weakness in patients with cervical spinal cord injuries [18] and in males over 60 years old [19].  
During the compression phase (Figure 1c), cough reflex nerve impulses cause glottal closure and forceful contraction of the expiratory muscles. This compression phase normally lasts approximately 0.2 s. Furthermore, intrathoracic pressures during voluntary cough range from 58 to 214 cmH\({}_{2}\)O  
Figure 1: Four phases of a cough [11]. (**a**) Irritation phase. (**b**) Inspiration phase. (**c**) Compression phase. (**d**) Expulsion phase. The blue arrows represent air flow. The black arrows represent movements of each part. The white arrows represent airway closure. The brown parts represent mucus and foreign material. The brown dots represent the movement of mucus and foreign material from the lower airway to the upper airway. Modified from [PERSON], [PERSON]: Respiration in health and disease, Philadelphia, 1972, WB Saunders.  
and are associated with the CPF [20]. To increase intrathoracic pressure for coughing, glottal closure and expiratory muscle strength are important. The maximal expiratory pressure (MEP), an index of expiratory muscle strength, is also associated with the CPF [18].  
In the expulsion phase (Figure 1d), the glottis opens together with continued contraction of the expiratory muscles, causing an expulsive flow of air from the lungs. Cough flow and dynamic airway compression cause very large shear forces on the airway walls. As a result, mucus and foreign material can be expelled from the lower airways to the upper airway[PERSON]  
As described above, CPF is a measure closely related to the four cough phases. Moreover, previous studies have shown that CPF is related to age, vital capacity (VC) [18, 19], height, weight [21], physical activity, sex [22], and hand grip strength [19].