C. G. A. Persson

On the use of absorbing discs to sample mucosal surface liquids

A common technique to sample airway mucosal ‘surface’ liquids is with absorbing discs of filter paper. The present study examined the efficacy of this technique by analysing tracheal liquids of control and capsaicin (0.1 nmol)‐exposed guinea‐pig airways. Mucosal fluids, obtained by topically applied discs or by a specific lavage procedure, and tracheal tissue were sampled. The animals had received FITC‐dextran (MW 70 kDa) intravenously and this specific plasma tracer was analysed in the sampled material. Under control conditions significantly more FITC‐dextran was found in the discs than in the tracheal lavage fluids (P < 0.001) despite the fact that the lavaged mucosal surface was much larger than that covered by the discs, Capsaicin significantly increased the content of FTTC‐dextran in all fluids sampled as well as in the airway tissue. In all cases concentrations of FITC‐dextran in the disc fluids did not differ much from that in the tissue samples. These data suggest that absorbing discs severely disturb the epithelial‐barrier function and sample subepithelial fluid and solutes including macromolecules. As demonstrated in this study by the elevated content of a plasma tracer molecule an inflammatory process may, nevertheless, be traced in the mixture of surface and tissue fluids that is sampled by the discs.

Topical vasoconstrictor (oxymetazoline) does not affect histamine-induced mucosal exudation of plasma in human nasal airways

Mucosal exudation of almost unfiltered plasma proteins, plasma‐derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine‐induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double‐blind, randomized, cross‐over and placebo‐controlled study with pretreatment with a single dose oxymetazoline chloride (5 μg or 50 μg; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min, and three histamine challenges were performed at 30‐min intervals during this period. The concentrations of two exudative indices, N‐alpha‐tosyl‐l‐arginine methyl ester (TAME)‐esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique.

Microvascular exudative hyperresponsiveness in human coronavirus-induced common cold.

BACKGROUND--The inflammatory response of the airway microcirculation in rhinitis and asthma may be recorded as luminal entry of plasma macromolecules (mucosal exudation). This study examines the exudative responsiveness of the subepithelial microvessels in subjects with and without common cold after inoculation with coronavirus. METHODS--The airway mucosa was exposed to exudative concentrations of histamine (40 and 400 micrograms/ml) before and six days after inoculation. To assess whether mucosal penetration of a topically applied agent was altered, nasal absorption of chromium-51 labelled ethylene diamine tetraacetic acid (51Cr-EDTA, MW 372) was also examined. A nasal pool technique kept the challenge and tracer solutes in contact with the same ipsilateral mucosal surface. Concentrations of albumin in lavage fluids were measured as an index of mucosal exudation of plasma. Nasal absorption of 51Cr-EDTA was determined by the cumulated 24 hour urinary excretion of radioactivity. RESULTS--Nine subjects developed common cold after coronavirus inoculation and 10 remained healthy. Histamine produced concentration dependent mucosal exudation of plasma in all subjects before and after coronavirus inoculation. In subjects with common cold, however, the histamine-induced mucosal exudation was significantly augmented compared with the group without common cold. This exudative hyperresponsiveness is not explained by an increased baseline exudation because the lavage regimen used produced comparably low baseline exudation in both groups of subjects, nor is it explained by an increased penetration of topical histamine because the ability of the nasal mucosa to absorb 51Cr-EDTA was not significantly increased in the subjects with common cold. CONCLUSIONS--An increased proclivity of the airway subepithelial microcirculation to respond with plasma exudation develops during coronavirus-induced common cold. This specific exudative hyperresponsiveness may be a feature of inflammatory airway diseases.

Effects of nicotine on the human nasal mucosa.

BACKGROUND--Topical application of nicotine and stimulation of tachykinin containing sensory nerves have been shown to produce mucosal exudation of plasma and derangement of the epithelial lining in guinea pig and rat airways. If this occurred in man these effects might contribute to the pathogenesis of airway disease. This study, performed in healthy volunteers without atopy, examined whether nicotine affects the plasma exudation response and the mucosal absorption permeability of the human nasal airway. METHODS--The acute effects of increasing topical doses of nicotine (0.08-2.0 mg) were examined (n = 8) on nasal symptoms (pain), mucosal exudation of plasma (albumin), mucosal secretion of mucin (fucose), and mucosal exudative responsiveness (histamine induced mucosal exudation of albumin). A separate placebo controlled study was carried out to determine whether frequent applications of the high dose of nicotine (2.0 mg given eight times daily for nine days) had any deleterious effects on the airway mucosa detectable as altered responses to histamine challenge. Both mucosal exudation of plasma (n = 12) and mucosal absorption of chromium-51 labelled EDTA (n = 8) were thus examined in nasal airways exposed to both nicotine and histamine. RESULTS--Nicotine caused nasal pain and produced dose dependent mucosal secretion of fucose but failed to produce any mucosal exudation of albumin. The exudative responsiveness to histamine was, indeed, decreased when the challenge was performed immediately after administration of acute doses of nicotine, whereas the responsiveness was unaffected when histamine challenges were carried out during prolonged treatment with nicotine. The nasal mucosal absorption of 51Cr-EDTA in the presence of histamine did not differ between subjects receiving either placebo or nicotine treatment for nine days. CONCLUSIONS--The results indicate that nicotine applied to the human airway mucosa produces pain and secretion of mucin, but inflammatory changes such as mucosal exudation of plasma and epithelial disruption may not be produced. Neurogenic inflammatory responses, which are so readily produced in guinea pig and rat airways, may not occur in human airways.

Effect of seasonal allergic rhinitis on airway mucosal absorption of chromium-51 labelled EDTA.

BACKGROUND--Hyperpermeability of the airway mucosa is thought to be characteristic of allergic rhinitis and asthma. Nine subjects with seasonal rhinitis caused by birch pollen were studied and the nasal mucosal absorption of chromium-51 labelled EDTA was examined both in an asymptomatic period before the season and late into the season when significant allergic rhinitis symptoms were present. METHODS--A nasal pool device was used to keep a concentration of the absorption tracer in contact with a larger part of the mucosa of the ipsilateral nasal cavity. Absorption was allowed for 15 minutes and measured as the radioactivity appearing in the 24 hour urine sample. RESULTS--The nasal absorption of 51Cr-EDTA in subjects with seasonal allergic rhinitis was less during active disease than before the season. CONCLUSIONS--An airway epithelial barrier that is subject to prolonged eosinophilic inflammation may not be disrupted but may rather increase its functional tightness.

Hypertonic saline increases secretory and exudative responsiveness of human nasal airway in vivo

Hypertonic saline (HS) is used in sputum induction studies. However, little is known about the physiological effects of HS on human airways in vivo. The present study takes advantage of the fact that the airway effects of topical challenges may be accurately examined in the readily accessible nasal airway. The present study specifically examines whether exposure to HS affects histamine challenge-induced exudation of plasma (α2-macroglobulin) and methacholine-induced secretion of mucin (fucose). Isotonic saline and HS (27 and 45 g·L−1), with and without concomitant histamine challenges, and with and without preceding methacholine challenges, were administered onto the nasal mucosa in 16 healthy subjects. Lavage fluid levels of α2-macroglobulin and fucose were analysed. Histamine produced a significant mucosal output of plasma (α2-macroglobulin). HS itself did not evoke exudation of α2-macroglobulin, but it significantly increased the plasma exudation effect of histamine. Methacholine produced a significant nasal mucosal output of fucose. HS also increased the mucin secretion (fucose), and it enhanced the secretory effect of methacholine. The authors concluded that hypertonic saline alone evokes mucinous secretion in human nasal airways in vivo and that it also enhances the exudative and secretory effects of histamine and methacholine, respectively. Through different mechanisms the HS exposure may also improve the recovery of soluble indices in human nasal airways. Whether or not the present findings are translatable to human bronchial airways remains to be examined.

Human nasal absorption of 51Cr‐EDTA in smokers and control subjects

Passive exposure to cigarette smoke has emerged as a significant risk factor in the development of asthma and allergic airways disease. The pathogenetic mechanisms are not known, but increased absorption across the airway epithelial lining has been suggested as one possible mechanism of this effect of cigarette smoke. This study examines the absorption‐permeability of the nasal epithelial lining in cigarette smokers and non‐smokers. For comparison, the effect of a detergent, dioctylsodium sulfosuccinate (DS), is also examined. A solution containing 51Cr‐EDTA (51‐chromium labeled ethylene diamine tetraacetic acid) (mol. wt. 372 Da) was instilled and maintained in the nasal cavity in six smokers and 12 non‐smokers for 15min. Urine was collected for 24 h after the instillation. The accumulated amount of excreted 5lCr‐EDTA was measured and expressed as millilitre nasal instillate. In six non‐smokers the procedure was repeated when DS has been added to the instillate. The median recovered amount of 51Cr‐EDTA in smokers 0.07 ml (range 0.04‐0.32) was not significantly different from that in non‐smokers 0.16 ml (0.01‐1.22). The recovered amount of 51Cr‐EDTA increased from a median of 0.18 ml (0.01‐1.22) to 1.13 ml (0.53‐1.80) after addition of the detergent (P= 0.028). We conclude that the nasal airway absorption‐permeability is not increased in smokers. Hence, passive exposure to cigarette smoke may not produce an impairment of airway barrier functions.