Ciliated airways

Assessment of aerosols and aerosol delivery devices requires accurate estimations of not only was the activity deposited in the limgs, but also in other regions such as oropharynx and stomach. For clearance measurements, such as mucociliary clearance, absolute estimates of activity are not required. Instead, the method should be able to confirm initial deposition of the aerosol to, primarily, the ciliated airways and provide good differentiation between central and peripheral regions to allow their respective clearances to be determined. Acquisition frame has to be sufficiently fast to allow clearance to be accurately followed, particularly during the fast initial clearance of aerosols from the lungs. 

Zabner J, Freimuth P, Puga A, Fabrega A, Welsh MJ. 1997. Lack of high affinity fiber receptor activity explains the resistance of ciliated airway epithelia to adenovirus infection. J. Clin. Invest. 100 1144 19... 

Sims AC, Baric RS, Yount B et al (2005) Severe acute respiratory syndrome coronavi-rus infection of human ciliated airway epithe-lia role of ciliated cells in viral spread in the conducting airways of the lungs. J Virol 79(24) 15511-15524... 

Svartengren K, Svartengren M, Philipson K, Barck C, Byhn G, Camner P. Clearance in small ciliated airways in allergic asthmatics after bronchial provocation. Respiration 1999 66 112-118. 

Zabner J, Zeiher BG, Friedman E, Welsh MJ. Adenovirus-mediated gene transfer to ciliated airway epithelia requires prolonged incubation time. J Virol 1996 70 6994-7003. 

Airway administration of a phospholipid detergent can also disrapt tight junctions between mature ciliated airway epithelial cells, and it has been demonstrated to increase adenovirus-mediated tiansgene expression in murine nasal epithelium (68). Whether this approach is applicable in either normal or injured lung is undeteimined. 

Recent studies in healthy subjects have suggested that a sizeable If action of particles deposited in the bronchiolar region is retained for more than 72-96 hr, and that these particles clear more similarly to alveolarly deposited particles. An increased deposition with retentions in the smallest ciliated airways is supported by the similarity in the clearance patterns from these airways, by healthy subjects, for particles inhaled by bolus and particles inhaled expemely slowly (0.05 L/sec), with an intermediate phase of continued clearance between 24 and 96 hr (17,54). From these studies, clearance in the smallest ciliated airways seems to be incomplete, with retentions of about 40% of the particles assumed to have been deposited in the tracheobronchial region, probably because of ineffective mucociliary transport and cough clearance in small airways. Clearance from the bronchiolar region may have features in common with alveolar clearance (65). This region may thus eonstitute a vulnerable zone in which small airway diseases eventually may arise after repeated exposures to noxious agents. 

Wolff RK, Tillquist H, Muggenburg BA, Harkema JR, Mauderly JL. Deposition and clearance of radiolabeled particles from small ciliated airways in beagle dogs. J Aerosol Med 1989 2 261-270. 

In contrast, the mechanical functions of airway surfactant are not well established. One of the functions is particle transport Irom the alveoli to the ciliated airways by a surface tension gradient (78,79), another is particle translocation toward the epithelium in airways. In the present chapter we will focus on the latter mechanical function of the airway surfactant film. 

The particle transport rate M t) is a function of the transport rate toward ciliated airways g t), the transport rate toward lymphatic drainage ln t) and intra-pulmonary transport rates Pi t) according to the list of intrapulmonaiy pathways given in the foregoing. 

Figure 4 Kinetics of the fractional transport rate g t) of 00,04 particles from the peripheral lungs toward ciliated airways and, subsequently, to larynx in humans and various experimental animal species monkeys, dogs, guinea pigs, three strains of rats (HMT, Fischer-344, Long-Evans), hamsters, and mice.

However, cytotoxic particles, such as Am/Pu02 showed a dose-dependent retardation of particle transport rates in rats (94). In addition, the transport rates of ultrafine particles, smaller than 0.1 pm in rats (75,76), and of particles larger than 5 pm in rats and dogs were less than those of particles in the size range 0.5-5 pm (95,96). From those observations it was concluded in the HRTM of ICRP-66 (2) that particle transport toward ciliated airways is independent of the particle material, as long as the material is not cytotoxic and as long as the particles are in the range 0.5- to 5-pm diameter. 

Figure 6 Cumulative efficiencies of clearance pathways of HMT rats versus dogs from the epithelial surface either toward ciliated airways or into and through the alveolar epithelial membrane.

---