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Dipartimenti di Scienze Motorie e Riabilitative e di Medicina Interna, Università di Genova, 16132 Genova; and Fisiopatologia Respiratoria, Azienda Ospedaliera S. Croce e Carle, 12100 Cuneo, Italy
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Reticular basement membrane (RBM) thickness and
airway responses to inhaled methacholine (MCh) were studied in
perennial allergic asthma (n = 11), perennial allergic
rhinitis (n = 8), seasonal allergic rhinitis
(n = 5), and chronic obstructive pulmonary disease (COPD, n = 9). RBM was significantly thicker in
asthma (10.1 ± 3.7 µm) and perennial rhinitis (11.2 ± 4.2 µm) than in seasonal rhinitis (4.7 ± 0.7 µm) and COPD
(5.2 ± 0.7 µm). The dose (geometric mean) of MCh causing a 20%
decrease of 1-s forced expiratory volume (FEV1) was
significantly higher in perennial rhinitis (1,073 µg) than in asthma
(106 µg). In COPD, the slope of the linear regression of all values
of forced vital capacity plotted against FEV1 during the
challenge was higher, and the intercept less, than in other groups,
suggesting enhanced airway closure. In asthma, RBM thickness was
positively correlated (r = 0.77) with the dose
(geometric mean) of MCh causing a 20% decrease of FEV1 and
negatively correlated (r = 
0.73) with the forced
vital capacity vs. FEV1 slope. We conclude that
1) RBM thickening is not unique to bronchial asthma, and
2) when present, it may protect against airway narrowing and air trapping. These findings support the opinion that RBM thickening represents an additional load on airway smooth muscle.
airway responsiveness; remodeling; asthma; chronic obstructive pulmonary disease; rhinitis
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THICKENING OF THE RETICULAR basement membrane (RBM) has been described as a characteristic feature of airway remodeling in asthma (26), although it has also been observed in subjects with asymptomatic airway hyperresponsiveness (8, 19). Modeling studies (17, 27) have suggested that RBM thickening may represent an increased load on airway smooth muscle, thus limiting its shortening and opposing airway narrowing. On the other hand, RBM thickening may reduce the number of mucosal folds that form when ASM shortens, which would favor airway narrowing (30). The available experimental data (3, 9, 10) seem to support the latter prediction, although studies relating RBM thickening to severity of disease are conflicting (9, 10, 11). The assessment of the functional effects of RBM thickening in asthma may be complicated by the concomitant effects of several confounding factors, such as presence of inflammatory cells and mediators in the airways, atopic status, and allergen exposure.
In this study, we reasoned that, if RBM prevalently acts as a load contrasting airway smooth muscle shortening in vivo, then its thickening should reduce airway narrowing and occurrence of air trapping on exposure to a bronchoconstrictor agent. This hypothesis was tested in four groups of patients affected by bronchial asthma, perennial rhinitis, seasonal rhinitis, and chronic obstructive pulmonary disease (COPD), conditions in which airway hyperresponsiveness and airway remodeling may be variably associated.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects.
Thirty-three subjects participated in the study (Table
1). Of these, 11 were affected by mild
perennial asthma, 8 by perennial rhinitis without asthma, 5 by seasonal
rhinitis, and 9 by COPD. Allergic sensitization was assessed by a
standard skin prick test panel (Laboratorio Farmaceutico Lofarma,
Milan, Italy) and radioallergosorbent test (RAST; Pharmacia, Uppsala,
Sweden), including mites, cladosporium, alternaria, grasses, parietaria, olive, cypress,
and cat and dog dander. All subjects with perennial rhinitis or asthma
were sensitized to house dust mite allergen only (RAST 3rd-to-4th
class), whereas those with seasonal rhinitis were only sensitized (RAST
4th class) to either grass (n = 2) or
parietaria (n = 3) and were studied during
pollen season. Rhinitic subjects never experienced symptoms that may be
related to asthma or airway hyperresponsiveness (6), whereas asthmatic subjects were variably affected by concomitant rhinitis. Diagnoses of asthma and COPD were made according to the
definitions given by the American Thoracic Society (1, 2).
All subjects classified as COPD had a history of chronic bronchitis,
and in none of them did the administration of 200 µg of salbutamol
increase 1-s forced expiratory volume (FEV1) by 
12% of control and >200 ml. Subjects with reduced, single-breath CO diffusion capacity were not included. At the time of the study, all
patients were in a stable clinical condition, and none of them was
taking regular treatment with steroids, cromolyn, or bronchodilator
drugs. Asthmatic and COPD subjects were using short-acting 
2-agonists on demand, which were avoided for 12 h
before the studies. Seasonal rhinitic subjects were using oral and
local antihistamine on demand, which were avoided for 5 days before studies. As they were studied during pollen season, treatment avoidance
was associated with occurrence of mild symptoms of rhinitis. The study
was approved by the institutional ethics committee, and each subject
gave written, informed consent.
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Protocol. All subjects attended the laboratory on 2 consecutive days to have airway responsiveness to methacholine (MCh; day 1) and bronchial biopsy (BB; day 2) performed. The eight subjects with perennial rhinitis and nine of those with asthma were also studied after an allergen inhalation challenge, the results of which are the object of a companion paper (12).
Lung function. All measurements were obtained by a Vmax 6200 system (SensorMedics, Yorba Linda, CA). On each occasion, the highest of three FEV1 and forced vital capacity (FVC) within 100 ml was retained. In two asthmatic and one COPD subject, FVC values were not retained because forced expiration was not sustained for >6 s. Forced expiratory maneuvers without a sharp peak flow were discarded.
MCh challenge. Solutions of MCh were prepared by adding distilled water to dry powder MCh chloride (Laboratorio Farmaceutico Lofarma). Aerosols were delivered by SM-1 Rosenthal breath-activated dosimeter (SensorMedics) driven by compressed air (30 psi) with 1-s actuation. The aerosol output at the mouth was 10 µl per actuation. Aerosols were inhaled during quiet tidal breathing. After 20 inhalations of saline as a control, the subjects inhaled double-increasing doses of MCh from 20 µg, until FEV1, measured 1 min after each dose, decreased below 80% of control value or the maximum dose of 1,200 µg was achieved. The double increments of dose were obtained by using two MCh concentrations (1 and 10 mg/ml) with appropriate numbers of breaths. A 3-min interval was allowed between dose increments. Airway responsiveness to MCh was estimated from the noncumulative dose causing a 20% reduction in FEV1 from control (PD20), calculated by interpolation between two adjacent points of the log dose-response curve. In subjects without a 20% reduction of FEV1, the last MCh dose was retained as the PD20.
BB. After premedication with atropine (0.5 mg im) and prometazine hydrochloride (50 mg im), oxibuprocaine (4% solution) was instilled into the nostrils. A fiber-optic bronchoscope (type 1T20, Olympus BF) was then passed through the nose or the mouth without endotracheal tube and, after local anesthesia of pharynx and airways, into the bronchi. Four biopsy specimens were taken from the right upper lobe distal bifurcation.
Tissue specimens were fixed in 10% formaldehyde at 4°C for 4 h, embedded in paraffin, cut at 5 µm with a rotative microtome, and stained with hematoxylin and eosin and toluidine blue. Biopsy specimens were discarded if they were too small or thin, incorrectly oriented, or had the RBM disrupted. For cell counts (eosinophils and mast cells), bronchial mucosa was examined to a depth of 100 µm from the basement membrane over adjacent, non-overlapping high-power fields (at ×500 magnification with the aid of an eyepiece graticule) until all of the available area was covered. For each quantification, three sections of each specimen were examined, and cells were expressed as number per square millimeter of submucosa. Mast cells were examined at ×1,000 magnification to detect ongoing degranulation (granules surrounding the cell or crossing the cell membrane). The intraobserver mean coefficient of variation for three repeated measurements was 9% for eosinophils and 8% for mast cells. In two COPD cases, analysis to a depth of 100 µm was not possible, and inflammatory cells were not valuable. The thickness of RBM was measured on hematoxylin- and eosin-stained preparations by light microscope image analysis (Q 500, Leica, Cambridge, UK) at ×400 magnification from the base of bronchial epithelium to the outer limit of the reticular lamina, at regular intervals (20 µm), until at least 40 readings were obtained. The intraobserver mean coefficient of variation for three replicate measurements was 3%.Data analysis. Occurrence of air trapping during airway narrowing was inferred from the linear regression of the FVC values recorded at each step of the challenge against the corresponding FEV1 values. In this analysis, the slope value quantifies the amount of air trapping associated with airway narrowing, with a value of zero indicating airway narrowing with no air trapping.
Differences among groups were assessed by ANOVA with Duncan post hoc comparisons when values were normally distributed and by Kruskal-Wallis ANOVA by ranks when they were not normally distributed. The relationships between airway responsiveness and air trapping to RBM thickness were assessed by calculating Pearson's coefficient of correlation. Statistical significance was considered at P values <0.05. Data are presented as means ± SD, geometric means, or medians with upper and lower quartiles.| |
RESULTS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Lung function and BB data are presented in Table
2. In asthma, baseline FEV1
as percentage of predicted and FEV1/FVC were significantly
lower (P < 0.05) than in perennial rhinitis and higher
than in COPD (P < 0.01) but not significantly
different from seasonal rhinitis (P > 0.1 for both
comparisons). Furthermore, there were no differences between perennial
and seasonal rhinitis (P > 0.1 for both comparisons).
In COPD, baseline FEV1 percentage and FEV1/FVC
were significantly less than in any other groups (P < 0.01 for all comparisons).
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MCh-PD20 was significantly less in asthma than in perennial
rhinitis (P < 0.01), indicating greater airway
responsiveness in the former. A FEV1 decrease >20%
of control was achieved at MCh doses <1.2 mg in all asthmatic
subjects but in only two subjects with perennial rhinitis. No other
comparison of MCh-PD20 was statistically significant among
groups (P > 0.06 for all comparisons). The slope of
FVC vs. FEV1 (Fig. 1 and
Table 2) was significantly steeper in COPD than in asthma and perennial
rhinitis (P < 0.05 for both), whereas the intercept
was less than in perennial and seasonal rhinitis (P < 0.05 for both).
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The thickness of RBM was not significantly different (P > 0.3) between asthma and perennial rhinitis. In both groups, however, RBM was thicker than in COPD and seasonal rhinitis (P < 0.01 all comparisons) and above the reported normal range (28).
In asthma, RBM thickness positively correlated with
MCh-PD20 (r = 0.77, P < 0.01; Fig. 2) and negatively with the
slope of FVC vs. FEV1 (r = 0.73,
P < 0.03; Fig. 3). These
relationships suggest that the thicker the RBM, the less the airway
responsiveness and the less the occurrence of air trapping. In
perennial rhinitis, there was a narrow range of near-normal
MCh-PD20 values, despite a wide range of increased RBM
thickness values. By contrast, in seasonal rhinitis and COPD,
MCh-PD20 values were widely variable and occasionally (3 rhinitic and 3 COPD subjects) below the normal range, despite a narrow
range of near-normal RBM thickness values.
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Eosinophil numbers were not significantly different among groups (P > 0.5 for all comparisons). Mast cell number was higher in asthma and perennial rhinitis than in COPD and seasonal rhinitis (P < 0.01 for all comparisons). The percentage of degranulating mast cells, i.e., with granules surrounding or crossing cell membrane, was greater in seasonal rhinitis than in perennial rhinitis and in asthma (P < 0.01). No significant correlation was found between RBM thickness and inflammatory cell numbers in bronchial mucosa in any group.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The major findings of the present study are that 1) RBM thickening is not unique to bronchial asthma, as it also occurs in subjects with perennial rhinitis without asthma, and 2) when present, RBM thickening is associated with less airway narrowing and air trapping in response to inhaled MCh. These findings would support the opinion that RBM thickening represents an additional load on airway smooth muscle.
Comments on methodology. Our analysis of the effects of MCh on airway narrowing and air trapping is based on the assumption that total lung capacity does not change during the challenge (24), and, therefore, any decrease in FVC reflects an increase in residual volume and, by inference, air trapping (13). In contrast, a decrease in FEV1 is assumed to reflect airway narrowing at the level of the flow-limiting segment, or an increase in frictional losses at high-lung volume, or both (21). It is possible that changes in FVC and in FEV1 are determined by mechanisms occurring at different levels along the bronchial tree. Therefore, their comparison with results of bronchial biopsies taken in large airways assumes that airway remodeling in these airways is also representative of remodeling in more distal airways (25). Furthermore, in this study, biopsy specimens were taken at a single site and assumed to be representative of airway remodeling throughout the lung. This assumption seems to be justified by the findings of Bradley et al. (4) and Jeffery et al. (15).
Comments on results. The occurrence of subepithelial fibrosis in asthma was first reported by Roche et al. (26) more than a decade ago and ever since has been considered as a characteristic feature of bronchial asthma (9, 16). The results of the present study indicate that RBM thickening is not unique to bronchial asthma, as it also occurs in subjects with perennial allergic rhinitis who never suffered from asthma symptoms. The findings of RBM thickening in both perennial asthma and rhinitis, but not in seasonal rhinitis and COPD, would suggest that subepithelial fibrosis may result from IgE-mediated airway inflammation with prolonged exposure to the sensitizing allergen. This is in agreement with a recent animal study (23), in which long-standing exposure to the sensitizing agent was necessary to cause collagen deposition in the airways.
Although it must be kept in mind that a significant correlation does not prove a causal relationship, the relationships of MCh-PD20 and FVC vs. FEV1 slope to RBM thickness observed in asthma would suggest that subepithelial fibrosis may play a protective role against airway hyperresponsiveness and air trapping. This would be in keeping with the theoretical prediction that increased collagen deposition tends to increase airway wall stiffness, thus providing additional internal load on airway smooth muscle and limiting its linear shortening (7, 17). It has been theoretically predicted that maximal shortening of unloaded airway smooth muscle would result in complete airway closure (22). It has also been proposed that maximal airway smooth muscle shortening does not occur in vivo because of the elastic load imposed by lung elastic recoil (20). The negative relationship between air trapping (FVC vs. FEV1 slope) and RBM thickness found in asthma suggests that subepithelial fibrosis may be an additional, important factor limiting airway closure or extreme flow limitation. The flat relationships between RBM thickness and functional measurements (MCh-PD20 and FVC vs. FEV1 slope) observed in perennial rhinitis suggest that any degree of RBM thickening is sufficient to counteract the force developed by nonasthmatic airway smooth muscle. By contrast, the significant relationships found in asthma suggest that large RBM thickening is necessary to efficiently oppose the greater force generated by airway smooth muscle. Another theoretical prediction was that RBM thickening may influence the pattern of mucosal folding on airway smooth muscle shortening (30), with a thicker RBM corresponding to a reduced number of folds, thus resulting in a greater airway narrowing. However, according to a recent study, the number of mucosal folds is determined by the number of tethers between RBM and the smooth muscle layer, rather than RBM thickness itself (27). The finding of a different MCh-PD20, despite similar RBM thickening in asthma and perennial rhinitis, does not support the hypothesis that subepithelial fibrosis may contribute significantly to enhance airway narrowing. Others have reported a positive, although weak, correlation between airway responsiveness and RBM thickness in asthma (3, 10, 14). This inconsistency might be due to the confounding effect of additional mechanisms modulating airway narrowing, independent of the RBM thickening. Inflammatory cells and their mediators may be variably present in allergic subjects, depending on allergen exposure, thus possibly causing an increased sensitivity of airway smooth muscle to contractile stimuli. Furthermore, subepithelial fibrosis may be associated with the presence of myofibroblasts (5), whose contribution to force development is, however, undetermined. Airway responsiveness was occasionally increased in seasonal rhinitis but was always near normal in perennial rhinitis. Although the percentage of degranulating mast cells was greater in seasonal than in perennial rhinitis, their absolute numbers were similar. If the number of degranulating mast cells reflects the amount of mediators released in the airways and the airway smooth muscle of seasonal and perennial rhinitic subjects produces similar forces, it is possible that the lower airway responsiveness in the latter is somehow related to the protective effect of increased RBM thickness. This interpretation would be consistent with an animal study (23) in which airway hyperresponsiveness occurred after the first 2 wk of exposure to the sensitizing allergen, in association with an increase in airway inflammation, but waned in the subsequent 10 wk, when fibronectin and collagen deposition occurred in the airway wall. In COPD, the inhalation of MCh caused greater air trapping than in asthma, suggesting enhanced airway closure or extreme airflow limitation. Modeling studies (18) have shown that airway smooth muscle force is not a major determinant of airway narrowing in COPD. In these subjects, airway hyperresponsiveness may result from airway wall thickening (29) or reduced loads on airway smooth muscle (20). In the present study, the elastic recoil of the lung could not be determined. Therefore, possible effects of differences in the external elastic load on airway smooth muscle cannot be evaluated. Pulmonary emphysema was, however, unlikely to be present in our subjects, as those with reduced CO diffusion capacity were not included. It may be speculated that the enhanced air trapping in COPD is the result of an increased thickness of total airway wall but not of RBM. The apparent negative relationship between airway responsiveness and RBM thickening observed in asthma might have been due to a concomitant increase in lung elastic recoil in response to MCh. In a previous study, however, inhaled MCh did not affect the static pressure-volume curves of mild asthmatic subjects (24). Furthermore, in six subjects in whom the effect of deep inhalation was evaluated during the challenge (12), there was no significant correlation between the ability to dilate constricted airways by lung inflation and the thickness of RBM. In conclusion, even if it cannot be excluded that RBM thickening may limit the amount of inhaled bronchoconstrictor agents reaching airway smooth muscle, the findings of the present study seem to support modeling studies (17, 27), suggesting that RBM thickening may protect against airway narrowing by loading airway smooth muscle.| |
ACKNOWLEDGEMENTS |
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This study was supported in part by grants from Ministero dell'Università e della Ricerca Scientifica e Tecnologica (Rome, Italy) (to V. Brusasco and G. W. Canonica) and by Associazione per la Ricerca delle Malattie Immunologiche ed Allergiche (Genoa, Italy).
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FOOTNOTES |
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Address for reprint requests and other correspondence: V. Brusasco, Dipartimento di Scienze Motorie e Riabilitative, Università di Genova, Largo R. Benzi, 10, 16132 Genova, Italy (E-mail: brusasco{at}dism.unige.it).
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.
Received 29 November 2000; accepted in final form 9 April 2001.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
American Thoracic Society.
Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma.
Am Rev Respir Dis
136:
225-244,
1987[Web of Science][Medline].
2.
American Thoracic Society.
Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med
152:
S77-S121,
1995.
3.
Boulet, LP,
Laviolette M,
Turcotte H,
Cartier A,
Dugas M,
Malo J-M,
and
Boutet M.
Bronchial subepithelial fibrosis correlates with airway responsiveness to methacholine.
Chest
112:
45-52,
1997
4.
Bradley, BL,
Azzawi M,
Jacobson M,
Assoufi B,
Collins JV,
Irani A-M,
Schwartz LB,
Durham SR,
Jeffery PK,
and
Kay AB.
Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects and relationship to bronchial hyperresponsiveness.
J Allergy Clin Immunol
88:
661-674,
1991[Web of Science][Medline].
5.
Brewster, CEP,
Howarth PH,
Djukanovic R,
Wilson J,
Holgate ST,
and
Roche WR.
Myofibroblasts and subepithelial fibrosis in bronchial asthma.
Am J Respir Cell Mol Biol
3:
507-511,
1990.
6.
Burney, PGJ,
Chinn S,
Britton JR,
Tattersfield AE,
and
Papacosta AO.
What symptoms predict the bronchial response to histamine? Evaluation in a community survey of the Bronchial Symptoms Questionnaire (1984) of the International Union Against Tubercolosis and Lung Disease.
Int J Epidemiol
18:
165-173,
1989
7.
Carroll, NG,
Perry S,
Karkhanis A,
Harji S,
Butt J,
James AL,
and
Green FH.
The airway longitudinal elastic fiber network and mucosal folding in patients with asthma.
Am J Respir Crit Care Med
161:
244-248,
2000
8.
Chakir, J,
Laviolette M,
Boutet M,
Laliberté R,
Dubé J,
and
Boulet LP.
Lower airways remodeling in non asthmatic subjects with allergic rhinitis.
Lab Invest
75:
735-744,
1996[Web of Science][Medline].
9.
Chetta, A,
Foresi A,
Del Donno M,
Bertorelli G,
Pesci A,
and
Olivieri D.
Airways remodeling is a distinctive feature of asthma and is related to severity of disease.
Chest
111:
852-857,
1997
10.
Chetta, A,
Foresi A,
Del Donno A,
Consigli GF,
Bertorelli G,
Pesci A,
Barbee RA,
and
Olivieri D.
Bronchial responsiveness to distilled water and methacholine and its relationship to inflammation and remodeling of airways in asthma.
Am J Respir Crit Care Med
153:
910-917,
1996[Abstract].
11.
Chu, HW,
Halliday JL,
Martin RJ,
Leung DYM,
Szefler SJ,
and
Wenzel SE.
Collagen deposition in large airways may not differentiate severe asthma from milder forms of the disease.
Am J Respir Crit Care Med
158:
1936-1944,
1998
12.
Crimi, E,
Milanese M,
Oddera S,
Mereu C,
Rossi GA,
Riccio A,
Canonica GW,
and
Brusasco V.
Inflammatory and mechanical factors of allergen-induced bronchoconstriction in mild asthma and rhinitis.
J Appl Physiol
91:
1029-1034,
2001
13.
Gibbons, WJ,
Sharma A,
Lougheed D,
and
Macklem PT.
Detection of excessive bronchoconstriction in asthma.
Am J Respir Crit Care Med
153:
582-589,
1996[Abstract].
14.
Hoshino, M,
Nakamura Y,
Sim J,
Shimojo J,
and
Isogai S.
Bronchial subepithelial fibrosis and expression of matrix metalloproteinase-9 in asthmatic airway inflammation.
J Allergy Clin Immunol
102:
783-788,
1998[Web of Science][Medline].
15.
Jeffery, PK,
Godfred RW,
Ädelroth E,
Nelson F,
Rogers A,
and
Johansson S-A.
Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma.
Am Rev Respir Dis
145:
890-899,
1992[Web of Science][Medline].
16.
Jeffery, PK,
Wardlaw AJ,
Nelson FC,
Collins JV,
and
Kay AB.
Bronchial biopsies and asthma: an ultrastructural, quantitative study and correlation with hyperreactivity.
Am Rev Respir Dis
140:
1745-1753,
1989[Web of Science][Medline].
17.
Lambert, RK.
Role of bronchial basement membrane in airway collapse.
J Appl Physiol
71:
666-673,
1991
18.
Lambert, RK,
Wiggs BR,
Kuwano K,
Hogg JC,
and
Paré PD.
Functional significance of increased airway smooth muscle in asthma and COPD.
J Appl Physiol
74:
2771-2781,
1983
19.
Laprise, C,
Laviolette M,
Boutet M,
and
Boulet L-P.
Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodeling.
Eur Respir J
14:
63-73,
1999[Abstract].
20.
Macklem, PT.
A theoretical analysis of the effect of airway smooth muscle load on airway narrowing.
Am J Respir Crit Care Med
153:
83-89,
1996[Abstract].
21.
Mink, SN.
Mechanisms of reduced maximum expiratory flow in methacholine-induced bronchoconstriction in dogs.
J Appl Physiol
55:
897-912,
1983
22.
Moreno, RH,
Hogg JC,
and
Paré PD.
Mechanics of airway narrowing.
Am Rev Respir Dis
133:
1171-1180,
1986[Web of Science][Medline].
23.
Palmans, E,
Kips JC,
and
Pauwels RA.
Prolonged allergen exposure induces structural airway changes in sensitized rats.
Am J Respir Crit Care Med
161:
627-635,
2000
24.
Pellegrino, R,
Wilson O,
Jenouri G,
and
Rodarte JR.
Lung mechanics during induced bronchoconstriction.
J Appl Physiol
81:
964-975,
1996
25.
Roche, WR.
Inflammatory and structural changes in the small airways in bronchial asthma.
Am J Respir Crit Care Med
157:
S191-S194,
1998.
26.
Roche, WR,
Beasley R,
Williams JH,
and
Holgate ST.
Subepithelial fibrosis in the bronchi of asthmatics.
Lancet
1:
520-524,
1989[Web of Science][Medline].
27.
Seow, CY,
Wang L,
and
Paré PD.
Airway narrowing and internal structural constraints.
J Appl Physiol
88:
527-533,
2000
28.
Vignola, AM,
Chanez P,
Campbell AM,
Souques F,
Lebel B,
Enander I,
and
Bousquet J.
Airway inflammation in mild intermittent and persistent asthma.
Am J Respir Crit Care Med
157:
403-409,
1998
29.
Wiggs, BR,
Bosken C,
Paré PD,
James A,
and
Hogg JC.
A model of airway narrowing in asthma and in chronic obstructive pulmonary disease.
Am Rev Respir Dis
145:
1251-1258,
1993.
30.
Wiggs, BR,
Hrousisi AR,
Drazen JM,
and
Kamm RD.
On the mechanism of mucosal folding in normal and asthmatic airways.
J Appl Physiol
83:
1814-1821,
1997
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 D. M. Hyde, L. A. Miller, E. S. Schelegle, M. V. Fanucchi, L. S. Van Winkle, N. K. Tyler, M. V. Avdalovic, M. J. Evans, R. Kajekar, A. R. Buckpitt, et al. Asthma: a comparison of animal models using stereological methods Eur. Respir. Rev., December 1, 2006; 15(101): 122 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. An, B. Fabry, X. Trepat, N. Wang, and J. J. Fredberg Do Biophysical Properties of the Airway Smooth Muscle in Culture Predict Airway Hyperresponsiveness? Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 55 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bergeron and L.-P. Boulet Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest, April 1, 2006; 129(4): 1068 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. R. Henderson Jr., G. K. S. Chiang, Y.-t. Tien, and E. Y. Chi Reversal of Allergen-induced Airway Remodeling by CysLT1 Receptor Blockade Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 718 - 728. [Abstract] [Full Text] [PDF]
|
|
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|
 |
|
 S. J. Wadsworth, A. M. Freyer, R. L. Corteling, and I. P. Hall Biosynthesized matrix provides a key role for survival signaling in bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 2004; 286(3): L596 - L603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Niimi, H. Matsumoto, M. Takemura, T. Ueda, K. Chin, and M. Mishima Relationship of Airway Wall Thickness to Airway Sensitivity and Airway Reactivity in Asthma Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 983 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Barbato, G. Turato, S. Baraldo, E. Bazzan, F. Calabrese, M. Tura, R. Zuin, B. Beghe, P. Maestrelli, L. M. Fabbri, et al. Airway Inflammation in Childhood Asthma Am. J. Respir. Crit. Care Med., October 1, 2003; 168(7): 798 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Evans, M. V. Fanucchi, G. L. Baker, L. S. Van Winkle, L. M. Pantle, S. J. Nishio, E. S. Schelegle, L. J. Gershwin, L. A. Miller, D. M. Hyde, et al. Atypical development of the tracheal basement membrane zone of infant rhesus monkeys exposed to ozone and allergen Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L931 - L939. [Abstract] [Full Text] [PDF]
|
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|
|
 |
|
 V. Brusasco and R. Pellegrino Invited Review: Complexity of factors modulating airway narrowing in vivo: relevance to assessment of airway hyperresponsiveness J Appl Physiol, September 1, 2003; 95(3): 1305 - 1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. McParland, P. T. Macklem, and P. D. Pare Airway wall remodeling: friend or foe? J Appl Physiol, July 1, 2003; 95(1): 426 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Olman Epithelial Cell Modulation of Airway Fibrosis in Asthma Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 125 - 128. [Full Text] [PDF]
|
|
|
|
|
|
D. N. R. Payne, A. V. Rogers, E. Adelroth, V. Bandi, K. K. Guntupalli, A. Bush, and P. K. Jeffery Early Thickening of the Reticular Basement Membrane in Children with Difficult Asthma Am. J. Respir. Crit. Care Med., January 1, 2003; 167(1): 78 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Waters, P. H. S. Sporn, M. Liu, and J. J. Fredberg Cellular biomechanics in the lung Am J Physiol Lung Cell Mol Physiol, September 1, 2002; 283(3): L503 - L509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Palmans, R.A. Pauwels, and J.C. Kips Repeated allergen exposure changes collagen composition in airways of sensitised Brown Norway rats Eur. Respir. J., August 1, 2002; 20(2): 280 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Palmans, N. J. Vanacker, R. A. Pauwels, and J. C. Kips Effect of Age on Allergen-induced Structural Airway Changes in Brown Norway Rats Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1280 - 1284. [Abstract] [Full Text] [PDF]
|
|
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|
|
|
J. Latourelle, B. Fabry, and J. J. Fredberg Dynamic equilibration of airway smooth muscle contraction during physiological loading J Appl Physiol, February 1, 2002; 92(2): 771 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Crimi, M. Milanese, S. Oddera, C. Mereu, G. A. Rossi, A. Riccio, G. W. Canonica, and V. Brusasco Inflammatory and mechanical factors of allergen-induced bronchoconstriction in mild asthma and rhinitis J Appl Physiol, September 1, 2001; 91(3): 1029 - 1034. [Abstract] [Full Text] [PDF]
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), seasonal
rhinitis (
), and COPD (
), and
relationship of these variables between themselves in asthmatic
subjects (
). The significant correlation between MCh
noncumulative dose causing 20% reduction in FEV1 from
control (PD20) and RBM thickness in asthmatic subjects
suggests a protective role of RBM thickness against airway
hypersensitivity to MCh.
