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Elastic properties of the bronchial mucosa: epithelial unfolding and stretch in response to airway inflation

Physiology, School of Biomedical, Biomolecular, and Chemical Sciences, University of Western Australia, Perth, Australia

Submitted 28 April 2005 ; accepted in final form 10 July 2005

	ABSTRACT

TOP ABSTRACT METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
The bronchial mucosa contributes to elastic properties of the airway wall and may influence the degree of airway expansion during lung inflation. In the deflated lung, folds in the epithelium and associated basement membrane progressively unfold on inflation. Whether the epithelium and basement membrane also distend on lung inflation at physiological pressures is uncertain. We assessed mucosal distensibility from strain-stress curves in mucosal strips and related this to epithelial length and folding. Mucosal strips were prepared from pig bronchi and cycled stepwise from a strain of 0 (their in situ length at 0 transmural pressure) to a strain of 0.5 (50% increase in length). Mucosal stress and epithelial length in situ were calculated from morphometric data in bronchial segments fixed at 5 and 25 cmH₂O luminal pressure. Mucosal strips showed nonlinear strain-stress properties, but regions at high and low stress were close to linear. Stresses calculated in bronchial segments at 5 and 25 cmH₂O fell in the low-stress region of the strain-stress curve. The epithelium of mucosal strips was deeply folded at low strains (0–0.15), which in bronchial segments equated to 10 cmH₂O transmural pressure. Morphometric measurements in mucosal strips at greater strains (0.3–0.4) indicated that epithelial length increased by 10%. Measurements in bronchial segments indicated that epithelial length increased 25% between 5 and 25 cmH₂O. Our findings suggest that, at airway pressures <10 cmH₂O, airway expansion is due primarily to epithelial unfolding but at higher pressures the epithelium also distends.

mucosal folds; epithelium; airway mechanics

Folding properties of the epithelium relevant to ASM contraction have been widely studied (4–6, 10, 12). The mechanisms of mucosal expansion during lung inflation are less well documented. It is unclear whether expansion of the airway lumen is completely accounted for by unfolding of the epithelium or whether epithelial distension contributes to expansion of the airway wall under physiological pressures. An early study suggested that the mucosa was indistensible on the basis of findings that the epithelial length appeared constant when lungs were inflated or when airways narrowed as a result of ASM contraction (4). The basal lamina in blood vessels is also indistensible, suggesting that in the airway the basement membrane might restrict mucosal expansion (2). The apparent resistance of the epithelial membrane to stretch has allowed normalization of ASM to the length of the epithelium and airway size. However, other studies suggest that the epithelium may be distensible over physiologically relevant pressures. In human bronchial segments, McParland et al. (7) found evidence that the epithelium distends as much as 50% when airways are inflated to total lung capacity (TLC).

The capacity of the bronchial mucosa, including the epithelium, to distend over a range of pressures encountered in the lung depends on elastic properties of the mucosal membrane, which to our knowledge have not been reported. It was not possible to distinguish between elastic properties of epithelial cells and basement membrane, and we use the term "epithelium" in the context of its material properties to include both of these structures. The contributions of epithelial distension vs. unfolding at physiological pressures are also unclear. We assessed mucosal distensibility from strain-stress curves in mucosal strips and related this distensibility to epithelial length and folding. To relate epithelial morphology to stresses under physiological conditions, we used morphometric data from whole bronchial segments fixed at 5 and 25 cmH₂O luminal pressure to calculate the stress in the airway wall. Bronchial segments were also used to assess epithelial length at different pressures.

	METHODS

TOP ABSTRACT METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
Strain-stress curves and morphometry in mucosal strips.   Procedures conformed with the American Physiological Society’s "Guiding Principles in the Care and Use of Animals" and were approved by the institutional ethics and animal care unit. Pigs, >8 wk age, were sedated with tiletamine-zolazepam (4.4 mg/kg im) and xylazine (2.2 mg/kg) and then exsanguinated under pentobarbitone sodium (25 mg/kg iv) anesthesia. A 2- to 4-cm segment from the proximal end of a main stem bronchus (5 mm ID) was excised and placed in a petri dish under a dissecting microscope. Thus viewed, the in situ perimeter of the airway lumen, without interstices, was recorded with a digital camera attached to the microscope and measured using Optimus image analysis software (Media Cybernetics). The perimeter of the lumen was again recorded after the segment was cut longitudinally, a procedure that resulted in a reduction of perimeter as airway tissue retracted. The ratio of the lumen perimeter before to that after transection was used to set the resting length of the mucosal strips (see below). After transection, the airway was pinned mucosa side up, and a 1-mm-wide strip of mucosa was marked by cuts through the mucosa with a scalpel blade. Surgical silk threads (4-0) were tied around each end of the strip so that the knot-to-knot length of the strip was 1 cm after correction for tissue retraction (i.e., when the retracted mucosal strip was stretched back to its original in situ length in the airway at 0 transmural pressure). The strip was then carefully dissected from the bronchus, with as much loose connective tissue removed as possible. ASM was not removed to prevent physical damage to the mucosa. The preparation and orientation of the mucosal strips are shown in Fig. 1.

View larger version (22K): [in this window] [in a new window]   Fig. 1. Schematic of a bronchial segment showing dimensions used to calculate wall stress from the Laplace equation. Luminal (l) and adventitial (a) radii are shown. Bronchial segments were also used to provide mucosal strips, which were cut transversely across the airway. Length of the strip and length of the epithelium were recorded in morphometric studies. Additional measurements included thickness of the epithelium and number of folds.

Mucosal strips were first set to a length of 1 cm. After equilibration, the strip was lengthened to 1.5 cm and returned to 1 cm in 0.05-cm increments by means of a calibrated micrometer screw. A maximum increase in mucosal length of 50% was selected, because it allowed a plateau in the strain-stress curve to be recorded (see RESULTS). The change in force (in grams) at each length was measured after 90–95% of stress relaxation had occurred (2 min). Each strip was subjected to three cycles. Because the second and third curves were approximately the same, the third was used for analysis. Stress was calculated from change in force and the cross-sectional area (i.e., force/cross-sectional area). Cross-sectional area was determined from the volume and length of each strip. Volume was measured by isolating the length between each silk tie and weighing the segment, with the assumption that the density of the tissue was 1 g/cm³. Strain in mucosal strips was determined from the change in tissue length and the initial in situ length of mucosa (i.e., L/L_i).

Trachea mucosal strips were prepared as described for bronchi, except they were excised from the area of the trachea opposing the smooth muscle to ensure that there was no muscle in the preparation.

In a separate experiment, mucosal strips were fixed at different lengths to determine the effect of stretch on the length and thickness of the epithelium and on epithelial folding. For this purpose, contiguous strips were pinned onto small pieces of cork board and then fixed in 4% formaldehyde solution. To aid accurate and secure pinning of the strips, the two ends of each strip were ligated with surgical silk as described above to obtain a knot-to-knot length of mucosa that in situ was 1 cm long. One strip was pinned at this 1-cm length (i.e., 0 strain). Others were stretched to 1.15 cm (0.15 strain), 1.30 cm (0.3 strain), and 1.4 cm (0.4 strain) when pinned. Tissue dissection, ligation, and stretching were carried out under a dissecting microscope, and lengths were set with fine calipers. The above-described process was repeated at two to three closely positioned regions of each of three bronchi (3 pigs in total). After fixation for >24 h, strips were processed into wax while they remained attached to the cork. Before they were blocked, the strips were freed from the cork by cuts between the knots and then set in wax blocks. Removal of the silk knots at each end of the strip resulted in a final processed length that was slightly shorter than the original fresh knot-to-knot length. An adjustment for this discrepancy was incorporated into subsequent morphometry (see below). Sections (8 µm thick) were prepared from the longitudinal plane of each strip, such that the epithelium could be seen in profile. Sections were stained with Verhoeff and Van Giesson stains for visualization of collagen and elastin fibers.

The following averaged measurements were made on duplicate sections of bronchial strips using Optimus image analysis software: 1) length of the mucosal strip (Fig. 1), 2) length of the luminal border of the epithelium, including folds, as a measure of epithelial length (Fig. 1), 3) thickness of the epithelium, including basal cells, and 4) number of epithelial folds per millimeter epithelial length. The epithelial length used in measurements 2 and 4 was first corrected for loss of some tissue from the ends of each strip during tissue processing for histology (see above) by multiplying the epithelial length, measured in each section, by the ratio of the original known length of the stretched mucosal strip (i.e.. 1, 1.15, 1.3, or 1.4 cm) to the length of the mucosal strip measured in the histological section.

Perimeter of the epithelium in fixed airways.   The effect of luminal pressure on the internal perimeter (P_i) of the epithelium (1) was evaluated using bronchial segments (2 mm ID) prepared for a previous publication (8). Bronchial segments were removed from 13 pig lungs and mounted in organ baths similar to those used for the tissue length-force measurements described above. However, the lumen was connected to a pressure reservoir containing Krebs solution, allowing the transmural pressure to be set at a predetermined value. The airway length was fixed so that increasing luminal pressure affected only the bronchial circumference. Airways were fixed in 4% formaldehyde solution after inflation to 5 or 25 cmH₂O luminal pressure.

After >12 h of fixation, a 0.5-cm segment from the midregion of each bronchus was processed and embedded in wax blocks for histology. At least four 8-µm transverse sections were cut from each blocked airway, with 0.5 mm between each section, and they were stained with hematoxylin and eosin. P_i was measured by tracing around the luminal perimeter of the folded epithelium using a microscope and Optimus software.

Because P_i could not be measured at different inflation pressures in the same airway, it was necessary to ensure that similar-sized airways were used in the two groups (5 and 25 cmH₂O). Accordingly, airway samples were taken from age-matched animals and from the same anatomic location (i.e., generation) in the stem bronchus of each animal. The total wall area was determined by morphometry, because we reasoned that this measurement would help determine whether airways were originally of similar size. Total wall area was slightly but significantly less at 25 than at 5 cmH₂O (Table 2). Because larger airways have a greater wall area (4), this finding suggested that an increased P_i, found at higher pressures (see RESULTS), was not due to systematic bias in airway sampling at the two pressures.

View larger version (24K): [in this window] [in a new window]   Fig. 2. Strain-stress relations in mucosal strips from bronchus (A) and trachea (B). Strain in mucosal strips was calculated as follows: change in tissue length ÷ initial in situ length of mucosa (i.e., L/Li). Inflation and deflation curves are shown, with inflationary curves at right. Values are means ± SE (n = 6–8). See Table 1 for compliances.

From the Laplace equation

where T is wall tension, P is luminal pressure, and r is luminal radius, given that

where is stress, F is force, L is airway length, and t is wall thickness and

and then substituting

Measurements are shown in Fig. 1. Wall thickness and luminal and adventitial radii were calculated using morphological data in bronchial segments fixed at 5 or 25 cmH₂O (see above). Wall thickness was calculated from the difference between outer airway radius (determined from total cross-sectional area of the airway) and luminal radius (calculated from luminal cross-sectional area). Using the luminal radius, we calculated wall stress at the inner curvature of the airway. However, because the airway wall is thick, this approach may be oversimplified. Furthermore, the analysis assumes that the different components of the wall had uniform material properties. The strain at these stresses was determined from the mucosal strip data by nonlinear regression.

Strain-stress data in mucosal strips closely fitted a two-phase exponential equation (R² > 0.98) of the following form

where is strain, is stress, and A, B, C, k, and l are fitting parameters.

Multiple comparisons were carried out by one-way ANOVA using GraphPad Prism software with Newman-Keuls post hoc test. Student’s t-test was used for single comparisons. P < 0.05 was regarded as significant. Values are means ± SE. Except where stated, one mucosal strip or bronchus was used from each pig.

	RESULTS

TOP ABSTRACT METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
Strain-stress curves for the bronchial and tracheal mucosal strips are shown in Fig. 2. In bronchial and tracheal mucosal strips, strain rose rapidly with low stress and then approached a plateau at above 100 g/cm². Accordingly, strain-stress curves were partitioned into low- and high-stress regions (Table 1). At low strains and stresses, compliance was greater during deflation than during inflation. However, at high strains and stresses, compliance was less during deflation than during inflation. There were no differences in compliance of tracheal or bronchial preparations. Hysteresis was observed for all strips, with longer strain during deflation than during inflation at any stress.

View larger version (89K): [in this window] [in a new window]   Fig. 3. Histology of mucosal strips of bronchus at strains of 0 (A and B) and 0.4 (C and D). Verhoeff and Van Giesson stain show dense collagen (light gray, Coll) and elastic fibers (black/dark gray, Elast) between epithelium and airway smooth muscle (ASM). Mucosal strips were prepared as shown in Fig. 1. Elastic fibers are predominantly seen running transversely, i.e., along airway longitudinal plane. Scale bars: 1 mm (A and C) and 0.1 mm (B and D).

View larger version (14K): [in this window] [in a new window]   Fig. 4. Morphometry of bronchial mucosal strips. Mucosal strips were stretched to strains of 0, 0.15, 0.3, and 0.4 before fixation. A: length of epithelium. B: thickness of epithelium. C: number of epithelial folds normalized for length of epithelium. Values are means ± SE (n = 7). ##P < 0.01; ###P < 0.001 vs. 0.0.

Measured P_i was >20% greater in bronchial segments fixed at 25 cmH₂O than in generation-matched segments fixed at 5 cmH₂O (Table 2, Fig. 5). Inner wall stress (calculated above) was used to estimate the corresponding strain on mucosal strips at these pressures using the measured strain-stress properties of mucosal strips. At 5 cmH₂O the calculated mucosal strain was 0.08 ± 0.02, whereas at 25 cmH₂O the expected strain was 0.31 ± 0.05. The percent change in mucosal length implied by these expected strains was similar to the measured change in P_i of fixed bronchi (Fig. 5); i.e., the mucosal strips stretched from 1.08 times their in situ length at 0 transmural pressure to 1.31 times their in situ length (a 21% increase in length). The expected change in epithelial length for inflation from 5 to 25 cmH₂O was also estimated by interpolation of epithelial length at mucosal strains of 0.08 and 0.31 from data in Fig. 4A relating epithelial length to mucosal stretch. The expected change in epithelial length for inflation of bronchi from 5 to 25 cmH₂O was 10%, which is less than the change in P_i observed for the same inflation of bronchial segments (Fig. 5).

View larger version (17K): [in this window] [in a new window]   Fig. 5. Circumferential stretch (%increase) of airway wall preparations at luminal pressures of 5–25 cmH2O. A: increase in length of internal perimeter (Pi) in whole bronchial segments fixed at 25 cmH2O compared with those fixed at 5 cmH2O, as measured by morphometry. Morphometric data from which this value was obtained are given in Table 2. B: increase in length of mucosal strips at stresses calculated at luminal pressures of 5–25 cmH2O, regressed from inflationary strain-stress curves shown in Fig. 2. C: length of epithelium in mucosal strips at stresses calculated at airway pressures of 5–25 cmH2O, interpolated from relation between mucosal strain and length of epithelium shown in Fig. 4. Values are means ± SE (n = 6–7). ###P < 0.0001 vs. bronchial segments (1-sample t-test).

	DISCUSSION

TOP ABSTRACT METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

We identified the physiological relevance of the low-stress high-compliance and high-stress low-compliance regions of the strain-stress relation by estimating the stress in the wall of an airway at pressures approximating functional residual capacity (5 cmH₂O airway luminal pressure) and TLC (25 cmH₂O). Our approach, which was similar to that used by Gunst and Stropp (3) to calculate stress, used morphometric data from a previous study (8) in this laboratory in which pig airways were fixed while the lumen was pressurized to 5 and 25 cmH₂O. The Laplace equation used by us and others assumes an isotropic airway wall and applies principally to thin-walled cylindrical vessels. Because the airway wall is a thick, multilayered structure, the stress in the airway wall may vary from the ideal case. Also, our protocol measured static mechanical properties of the mucosa, and stress may vary under the dynamic conditions present in breathing (11). At 5 cmH₂O the stress was calculated to be 7.6 ± 0.6 g/cm², and at 25 cmH₂O it was 72.9 ± 4.0 g/cm². With use of these stresses, our analysis suggests that airway transmural pressures of 5 and 25 cmH₂O would produce inflationary strains of 0.08 and 0.31, respectively, in mucosal strips. The above findings suggest that under physiological conditions the low-stress high-compliance region of the strain-stress curve dominates mucosal mechanics.

A major aim was to investigate whether airway inflation can be accounted for solely by unfolding the epithelium or whether the epithelium also stretches with airway expansion. The structural basis of epithelial unfolding and stretch and the forces producing them are likely to be different, and each may make unique contributions to the elastic properties of the airway in health or disease. With respect to epithelial folding, the forces producing the folds are considered sufficient to exert physiological effects on airway narrowing (5, 6, 12). Little is known about the forces associated with stretching the epithelium or, indeed, whether the epithelium stretches under physiological pressures. Any changes in epithelial length on lung inflation are dependent on the elastic properties of the epithelium and its basement membrane, which were not partitioned in the present study. To assess unfolding and distension of the epithelium, mucosal strips were fixed at different strains and then examined morphometrically. In common with other studies in whole airways, epithelial folds were prominent at low strains (4, 5, 10) but were still present, but reduced, at strains equating to TLC (0.3–0.4 strain). After correcting the length of the tissue strip for loss of material in cutting and blocking (see METHODS), we were also able to measure the length of the epithelium, with folds and interstices taken into account. Because the initial length of the tissue samples (1 cm) was the same at all strains, the effect of stretching the mucosal strip on epithelial length could also be estimated. The thickness of the epithelium was also measured, inasmuch as we thought it would provide additional evidence for epithelial stretch. We showed that the length and thickness of the epithelium remained constant when the mucosal strip was stretched to a strain of 0.15, but at higher strains (0.3–0.4) the length of the epithelium increased. Although there was some suggestion that the epithelium became thinner as the mucosa was stretched, as it might if the length of the epithelium increased, this was not a statistically significant effect. A strain of 0.15, at which the epithelial length was unchanged, corresponds to the stress associated with 10 cmH₂O luminal pressure in a whole airway. Therefore, our findings suggest that, in the airways studied, luminal expansion is associated with unfolding of the epithelium at airway pressures (transmural pressure) up to 10 cmH₂O. This conclusion was further supported by the reduction in the number of folds in the epithelium when the mucosa was stretched. At pressures >10 cmH₂O the epithelium starts to distend or stretch as well as unfold. This pattern of airway expansion may differ in airways of different sizes or different locations and if structural properties of the airway change, for example, in airway remodeling. Previous studies provided conflicting data on the capacity of the epithelium to distend (as opposed to unfold) (4). However, a recent study suggested that the basement membrane has the capacity to stretch at physiological pressures (7). Previous and present findings provide strong evidence that the epithelium is distensible at physiological pressures, and we suggest that normalization of airway size by the luminal perimeter is not a reliable approach, particularly where airways are examined after different lung fixation pressures.

The capacity of the epithelium to distend on lung inflation was further assessed by measuring P_i in whole bronchial segments in which luminal pressure was increased to 5 or 25 cmH₂O before fixation. Clearly, the effect of increasing luminal pressure could not be measured in the same fixed airway specimen, necessitating the use of closely matched airway samples. With histological material used in a previous study (8), we compared P_i in airways of closely matched dimensions when uninflated, fixed at either pressure. Bronchi were taken from animals of the same body weight and at the same anatomic location and had the same luminal diameter at 0 cmH₂O as measured by gentle insertion of steel rods of known diameter into the distal and proximal ends of the lumen. Results showed that, at 5–25 cmH₂O luminal pressure, P_i increased by 25%, which is less than that recently reported by McParland et al. (7) in human airway segments. For comparison with mucosal strips, the difference in epithelial length was measured from the inflationary strains associated with 5 and 25 cmH₂O luminal pressure in an airway by interpolation of the relation between strain and epithelial length shown in Fig. 4. At a strain equating to 25 cmH₂O luminal pressure in an airway, the epithelium in mucosal strips was 10% longer than at 5 cmH₂O, a degree of stretch somewhat less than that observed in whole bronchial segments. We are unsure of the cause of the difference in epithelial distension between the whole airway and the mucosal strip, but it may relate to the airways used in our two studies. Mucosal strips were taken from large (5 mm ID) bronchi to obtain sufficient experimental material. Bronchial segments were more peripheral (2 mm ID), which may result in increased compliance of the epithelium and, consequently, greater stretch.

In conclusion, direct measurement of airway epithelium shows that epithelial length is not constant as the mucosa is stretched. At low stresses, corresponding to luminal pressures <10 cmH₂O, mucosal expansion occurs with unfolding of the epithelium, but at higher pressures similar to those achieved during maximal lung inflation, the increase in mucosal length is associated with epithelial unfolding and epithelial stretch. Over the full range of physiological pressures, the mucosa is in the low-stress linear region of its compliance curve.

	ACKNOWLEDGMENTS

TOP ABSTRACT METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
We thank A. Light for expert histological assistance.

	FOOTNOTES

 

Address for reprint requests and other correspondence: H. Mitchell, Physiology, School of Biomedical, Biomolecular, and Chemical Sciences, Univ. of Western Australia, 35 Stirling Hwy., Crawley, Western Australia 6009 (E-mail: mitchell{at}cyllene.uwa.edu.au)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

	REFERENCES

TOP ABSTRACT METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 

1. Bai A, Eidelman DH, Hogg JC, James AL, Lambert RK, Ludwig MS, Martin J, McDonald DM, Mitzner WA, Okazawa M, Pack RJ, Pare PD, Schellenberg RR, Tiddens HAWM, Wagner EM, and Yager D. Proposed nomenclature for quantifying subdivisions of the bronchial wall. J Appl Physiol 77: 1011–1014, 1994.[Abstract/Free Full Text]
2. Cook TA, Salmo NA, and Yates PO. The elasticity of the internal lamina. J Pathol 117: 253–258, 1975.[CrossRef][Web of Science][Medline]
3. Gunst SJ and Stropp JQ. Pressure-volume and length-stress relationships in canine bronchi in vitro. J Appl Physiol 64: 2522–2531, 1988.[Abstract/Free Full Text]
4. James AL, Pare PD, and Hogg JC. Effects of lung volume, bronchoconstriction and cigarette smoke on morphometric airways dimension. J Appl Physiol 64: 913–919, 1988.[Abstract/Free Full Text]
5. Lambert RK. Role of bronchial basement membrane in airway collapse. J Appl Physiol 71: 666–673, 1991.[Abstract/Free Full Text]
6. Lambert RK, Pare PD, and Okazawa M. Stiffness of peripheral airway folding membrane in rabbits. J Appl Physiol 90: 2041–2047, 2001.[Abstract/Free Full Text]
7. McParland BE, Pare PD, Johnson PR, Armour CL, and Black JL. Airway basement membrane perimeter in human airways is not a constant: potential implications for airway remodeling in asthma. J Appl Physiol 97: 556–563, 2004.[Abstract/Free Full Text]
8. Noble PB, McFawn PK, and Mitchell HW. Intraluminal pressure oscillation enhances subsequent airway contraction in isolated bronchial segments. J Appl Physiol 96: 1161–1165, 2004.[Abstract/Free Full Text]
9. Okazawa M, Pare PD, and Lambert RK. Compliance of peripheral airways deduced from morphometry. J Appl Physiol 89: 2373–2381, 2000.[Abstract/Free Full Text]
10. Okazawa M, Vedal S, Verburgt L, Lambert RK, and Pare PD. Determinants of airway smooth muscle shortening in excised canine lobes. J Appl Physiol 78: 608–614, 1995.[Abstract/Free Full Text]
11. Wang L, Tepper R, Bert JL, Pinder KL, Pare PD, and Okazawa M. Mechanical properties of the tracheal mucosal membrane in the rabbit. I. Steady-state stiffness as a function of age. J Appl Physiol 88: 1014–1021, 2000.[Abstract/Free Full Text]
12. Wiggs BR, Hrousis CA, Drazen JM, and Kamm RD. On the mechanism of mucosal folding in normal and asthmatic airways. J Appl Physiol 83: 1814–1821, 1997.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Free All Versions of this Article: 99/6/2061    most recent 00485.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Noble, P. B. Articles by Mitchell, H. W. Search for Related Content PubMed PubMed Citation Articles by Noble, P. B. Articles by Mitchell, H. W.