J Appl Genetics (2011) 52:39–51 Fig. 2 The pseudostratified res- piratory epithelium (RE). a Localization in human airways; inset shows localization in the nasal cavity and the dashed lines encircle areas where the pseudostratified RE is localized. b Structure of the pseudostratified RE 43 uniform; for example, goblet cells are especially frequent in the regions of high air flow (Schmidt et al. 1998). Pseudostratified RE specimens for initiating primary cultures can be theoretically collected from any segment of the conducting airways, but not all of the segments are equally accessible and useful. Bronchial biopsies are relatively hard to obtain (surgical intervention is necessary) and often contam- inated with infectious agents (Wu et al. 1985). Nasal polyps, the most frequently exploited, easily accessible abundant source of the respiratory tissue, show defects in ion transport (increased Na+ absorption and Cl− permeability) and cannot be used for studies of drug permeation and metabolism in nasal epithelium (Schmidt et al. 1998). Normal epithelial tissue collected from the nasal cavity allows overcoming of the above-mentioned restrictions. In the nose, the pseudostratified RE occupies the central part of the nasal cavity, bordered by the squamous and transitional epithelium in the nasal anterior, and by the olfactory epithelium in the upper part of the cavity (Mygind and Dahl 1998) (Fig. 1a inset). The tissue in the central part of the nasal cavity expresses important features of the lower airway RE, and is relatively easily accessible, allowing sampling to be performed in the ambulatory settings. There are three different groups of techniques used for the sampling of the nasal epithelium: traumatic methods, atrau- matic methods, and postmortem biopsies (Schmidt et al. 1998). Traumatic methods include surgical biopsy, surgical removal of nasal polyps (polypectomy), or nasal turbinates (turbinectomy), as well as plastic surgery (face reconstruc- tion). The biggest advantage of these methods is the usually high amount of harvested cells (Schmidt et al. 1998). This is reflected in the literature, where most of the primary epithelial cell cultures are started by the use of traumatic techniques. The main disadvantage is that these techniques require at least local anesthesia, and that collecting samples from the same area of the nose can rarely be repeated (Schmidt et al. 1998). Postmortem biopsies are similar to the traumatic methods in their advantages and shortcomings. They provide a high harvest of epithelial cells, but repeated sampling is not possible. In addition, artifacts caused by medication, stress, and variable ischemia time can exist (Schmidt et al. 1998). In contrast, atraumatic sampling techniques do not require anesthesia and they offer the possibility to repeat the tissue sampling (Bridges et al. 1991a, b). In addition, material can be sampled from a precise area of the nasal cavity (Schmidt et al. 1998). Among many methods of