Lung airways structure

The role of neuronal NOS in the airways is incompletely understood. The gene encoding the enzymes has been isolated and cloned (Bredt et al., 1991), and a strain of neuronal NOS knockout mice has recently been developed (Huang etal., 1993 O Dell etal., 1994). WhUe these mice had pyloric stenosis (a characteristic that reaffirmed the important role of iNOS in gastrointestinal neurotransmission), they had no obvious abnormalities of airway structure. The relevance of these findings to the human airway remains to be determined, and the data need to be considered in light of the diverse bioactivities of NO in the lung. 

Having discussed relevant aspects of lung and airway structure that may influence the efficacy of aerosol therapy, it is important that we consider the potential impact of differences in respiratory function between individuals as a result of age, maturity, or clinical status. Particular problems may be encountered in delivering drugs to the respiratory tract of young children as a result of anatomic and physiological variations due to age (198). The most relevant aspects of respiratory physiology with respect to aerosol therapy include the... 

The in vivo data presented above are also limited to studies involving healthy volunteers and as such say little about the relationship between in vitro characteristics and deposition profiles in diseased airways. However, it does appear that in general total deposition is similar, but profiles within the lung are changed in disease. Correlations between in vitro data and deposition in children and infants have also not been discussed. Because of the different airway structure in young children and the different breathing profiles, deposition patterns and the relationships between laboratory and clinic are likely to be different. 

In the lung, tissue engineering strategies have been employed to engineer larger airway structures such as the trachea, main stem bronchi, and bronchiole. In 2008, the first transplantation of a tissue-engineered trachea in a human being... 

During development from infancy to adulthood, the respiratory system undergoes substantial changes in airway structure and lung volume, accompanied by considerable differences in spontaneous-breathing conditions (198-206). Even in adults, distinct sex-related and racial differences are established for structural and conventional Imig function parameters (207-211). However, only limited... 

The conducting airways carry out two major functions. The first is to lead inspired air to the more distal gas-exchanging regions of the lungs. The second is to warm and humidify the inspired air as it flows through them. The alveoli are delicate structures and may be damaged by excessive exposure to cold, dry air. 

A variety of cell culture systems for the modelling of the tracheo-bronchial epithelium are available. These include primary cultures and cell lines of human and animal origins, plus airway cells with characteristics of lung disease such as CF. The advantages and limitations of using a simple culture system compared to one that recreates to a greater extent the epithelial structure and function in vitro should be considered according to the pre-clinical application required. However, this choice is complicated by the lack of comparative data, both between the different cell systems and for in vitro-in vivo correlation, upon which to base such decisions. 

Horsfield, K. The relation between structure and function in the airways of the lung. Brit. J. Dis. Chest 68 145-160, 1974. 

Bronchoalveolar lavage fluid (BALF) is presently the most common way of sampling components of the epithelial lining fluid and provides the most accurate reflection of pulmonary airway protein composition. Proteomic studies of BALF have already been published and have contributed to a better knowledge of the lung structure at the molecular level and the study of lung disorders at the clinical level [23]. 

The lung contains more than 40 different cell types, of which more than six line the airways (Figure 10.2). The diversity of pulmonary epithelia can be illustrated by examining its structure at three principal levels... 

The rate of protein clearance has been estimated as 10% of the rate of fluid clearance from alveoli [173]. IgG clearance is probably mediated by FcRn transcytosis in distal type I alveolar epithelium and more proximal bronchial epithelium. Type I alveolar epithelium and bronchial epithelium contain the necessary subcellular structures for FcRn-mediated transcytosis vesicles, membrane invaginations, caveolae, and clathrin-coated pits [173,174], FcRn mRNA is expressed in lung although the cell types and locations have not yet been determined [112], Moreover, primary alveolar epithelial monolayer cell cultures express functional FcRn [173], plgA-R/SC transcytosis is thought to contribute little to distal (alveolar) airway IgG transport but might mediate more proximal (bronchial or bronchiolar) IgA transport [173], Uptake of an aerosolized IgG Fc-erythropoietin fusion molecule and subsequent erythropoietin-induced reticulocytosis has been demonstrated in human and nonhuman primates [175],... 

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