Epithelial lining fluid

Cantin, A.M., Hubbard, R.C. and Crystal, R.G. (1989). Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract of patients with idiopathic pulmonary fibrosis. Am. Rev. Resp. Dis. 139, 370-372. 

It should be noted that the permeability per surface unit of alveolar epithelium per se is not particularly high. The significant absorption found for various substances after pulmonary administration is rather explained by a number of beneficial factors such as the large surface area of the alveoli, the low volume of the epithelial lining fluid, the relatively thin diffusion layer, the absence of mucociliary clearance from the alveoli as well as the limited enzymatic activity in the lining fluids. 

Proteases occurring in the epithelial lining fluids are another source of variability in protein absorption from the lung. In the epithelial lining fluids proteases and peptidases do occur. Inhibition of proteases and peptidases with substances such as bacitracin or aprotinin might improve the bioavailability of proteins. For example bacitracin was shown to increase insulin bioavailability by a factor of 6.8 [3]. 

In a 1-week study of cystic fibrosis patients treated with aerosolized native ai-PT, it was shown that Inhibitor levels reached 8 JUnol/L, which was sufficient to completely suppress NE activity in the epithelial lining fluid [69]. Such levels were reached in several patients who were rival 1.5-3 mg/kg native ai-PI every 12 boms. In the same study it was reported dial weekly intravenous doses of 120 mg/kg native ai-PI given over a time period of one month was not sufficient to suppress NE activity in epithelial lining fluid of cystic fibrosis patients. Hus study proved that ai-PI can be delivered active as an aerosol to the lung of patients and that concentration levels can be reached that are sufficient to inhibit... 

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]. 

Once in solution, the drug will diffuse through the mucus layer and enter the aqueous environment of the epithelial lining fluid. The rate of diffusion through the mucus will be dependent upon such factors as ... 

Mucociliary clearance is an organized, complex process which is highly dependent upon the composition and depth of the epithelial lining fluid and the viscoelastic properties of the mucus. In many airways diseases there is hypersecretion of mucus. This may cause an overloading of the ciliary transport process, resulting in... 

The exposure to hyperoxia for several days increases epithelial lining fluid (ELF) GSH levels, and tobacco smokers also show an increase in ELF GSH at a concentration of nearly twice the normal level [37,38]. On the contrary, reduced leukocyte concentration of GSH, Met and Cys and decreased urinary excretion of inorganic Sulphate are observed in severely burned patients [39]. 

A. Cantin, S. North, R. Hubbard and R. Crystal, Normal Epithelial Lining Fluid Contains High Levels on Glutathione, J Appl Physiol 63 (1987) 152-157. 

Langford, S.D., Bidani, A., Postlethwait, E.M. Ozone-reactive absorption by pulmonary epithelial lining fluid constituents. Toxicol Appl Pharmacol 732 (1995) 122-130. 

Once a drug aerosol has made its way through the conducting airways to deposit in the deep lung, the major barriers to entering the body are the 0.15 pm layer of type I alveolar cells that are covered by a very thin layer of epithelial lining fluid consisting mainly of surfactant and the relatively permeable endothelium of the alveolar capillaries. Alveolar cells have so called... 

AlAT) has been used in injectable form for the treatment of hereditary AlAT deficiency that markedly increases the risk of development of emphysema. Absorption of aerosolized human plasma and recombinant AlAT into the lymph and blood was studied in sheep and humans. Human plasma AlAT was found in the sheep blood and interstitial lymph at concentrations 1/1000 of that in the alveolar epithelial lining fluid (ELF). The recombinant human AlAT is non-glycosylated and has a terminal methionine residue. In the sheep model, this molecule disappears from the alveolar fluid faster than the human plasma AlAT, with the lymph levels around 10% of ELF and blood levels about 10% of the lymph. The recombinant form... 

In 17 patients aged over 18 years with severe acute community-acquired pneumonia trovafloxacin concentrations were persistently high in the sputum, bronchial secretions, bronchoalveolar lavage fluid, and epithelial lining fluid, with no significant difference between these compartments (16). The authors proposed that measurement of sputum concentrations could be used to monitor the outcome of treatment. 

Cantin AM, North SL. Hubbard RC, Crystal RG. 1987. Normal alveolar epithelial lining fluid contains high levels of glutathione. J. Appl. Physiol. 63 152-57... 

Alpha 1 Antitrypsin in CF. Alpha 1 antitrypsin (a 1-AT) can inhibit neutrophil elastase in epithelial lining fluid (ELF), restore ELF antineutrophil elastase capacity, and also reverse the inhibitory effect of CF ELF on neutrophil Pseudomonas killing [116]. Furthermore, aerosolized secretory leukoprotease inhibitor can reduce neutrophil number and also neutrophil elastase in CF subjects [117]. For these reasons some have suggested a possible role for a 1-AT in CF. This concept requires further exploration before clinical introduction. The treatment is exceedingly expensive, so use without good documentation would be inappropriate. 

Recombinant SLPI has been aerosolized to individuals with cystic fibrosis, and its effect on the NE burden has been evaluated [82], Aerosol application of SLPI (100 mg/kg) twice daily for one week reduced active NE levels in airway epithelial lining fluid. However, aerosolization of 50 mg/kg SLPI failed to reduce NE activity probably due to the large amount of free elastase in the epithelial lining fluid of cystic fibrosis patients [82]. The half-life of SLPI in the lung after the first application of 100 mg/kg was approximately 5.5 hours. These data demonstrate that sufficient amounts of aerosolized SLPI can significantly reduce the elastase burden of the lung in cystic fibrosis patients. 

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