Changes In Airway Morphology Research Articles

Cephalometric assessment of changes in the upper airway after orthognathic surgery in patients with unilateral cleft lip and palate sequelae treated at the «Dr. Manuel Gea González» General Hospital

A cephalometric analysis of the upper airway in patients with cleft lip and palate sequelae who underwent orthognathic surgery was performed. The study aims to determine if changes in upper airway morphology occur. Study design: A retrospective, descriptive, open, comparative, and cross-sectional study with a sample of 28 patients with unilateral cleft lip and palate sequelae (UCLPS) was performed. The study sample consisted of 50% male and 50% female patients whose ages ranged between 16 and 29 years of age and averaged 19.32 years. Measurements were made on pre- and post-surgical lateral headfi lms. A total of 672 cephalometric measurements were made. The study’s fi ndings indicate that changes in the upper airway after bone mobilization techniques in orthognathic surgery do exist. Statistical signifi cance was set at p < 0.05 and was met on three of the assessed variables: upper pharynx (p = 0.001), bony pharynx dimension (p = .000), and nasopharyngeal depth (p = .000). Key words: Cephalometric analysis, upper airway, unilateral cleft lip and palate sequelae, orthognathic surgery, upper pharynx, bony pharynx dimension, nasopharyngeal depth.

Cephalometric and anthropometric data of obstructive apnea in different age groups

IntroductionPatients with obstructive sleep apnea syndrome usually present with changes in upper airway morphology and/or body fat distribution, which may occur throughout life and increase the severity of obstructive sleep apnea syndrome with age. ObjectiveTo correlate cephalometric and anthropometric measures with obstructive sleep apnea syndrome severity in different age groups. MethodsA retrospective study of cephalometric and anthropometric measures of 102 patients with obstructive sleep apnea syndrome was analyzed. Patients were divided into three age groups (≥20 and <40 years, ≥40 and <60 years, and ≥60 years). Pearson's correlation was performed for these measures with the apnea–hypopnea index in the full sample, and subsequently by age group. ResultsThe cephalometric measures MP-H (distance between the mandibular plane and the hyoid bone) and PNS-P (distance between the posterior nasal spine and the tip of the soft palate) and the neck and waist circumferences showed a statistically significant correlation with apnea–hypopnea index in both the full sample and in the ≥40 and <60 years age group. These variables did not show any significant correlation with the other two age groups (<40 and ≥60 years). ConclusionCephalometric measurements MP-H and PNS-P and cervical and waist circumferences correlated with obstructive sleep apnea syndrome severity in patients in the ≥40 and <60 age group.

Validation of airway wall measurements by optical coherence tomography in porcine airways.

Examining and quantifying changes in airway morphology is critical for studying longitudinal pathogenesis and interventions in diseases such as chronic obstructive pulmonary disease and asthma. Here we present fiber-optic optical coherence tomography (OCT) as a nondestructive technique to precisely and accurately measure the 2-dimensional cross-sectional areas of airway wall substructure divided into the mucosa (WAmuc), submucosa (WAsub), cartilage (WAcart), and the airway total wall area (WAt). Porcine lung airway specimens were dissected from freshly resected lung lobes (N = 10). Three-dimensional OCT imaging using a fiber-optic rotary-pullback probe was performed immediately on airways greater than 0.9 mm in diameter on the fresh airway specimens and subsequently on the same specimens post-formalin-fixation. The fixed specimens were serially sectioned and stained with H&E. OCT images carefully matched to selected sections stained with Movat’s pentachrome demonstrated that OCT effectively identifies airway epithelium, lamina propria, and cartilage. Selected H&E sections were digitally scanned and airway total wall areas were measured. Traced measurements of WAmuc, WAsub, WAcart, and WAt from OCT images of fresh specimens by two independent observers found there were no significant differences (p>0.05) between the observer’s measurements. The same wall area measurements from OCT images of formalin-fixed specimens found no significant differences for WAsub, WAcart and WAt, and a small but significant difference for WAmuc. Bland-Altman analysis indicated there were negligible biases between the observers for OCT wall area measurements in both fresh and formalin-fixed specimens. Bland-Altman analysis also indicated there was negligible bias between histology and OCT wall area measurements for both fresh and formalin-fixed specimens. We believe this study sets the groundwork for quantitatively monitoring pathogenesis and interventions in the airways using OCT.

Upper airway factors that protect against obstructive sleep apnoea in healthy older males.

The prevalence of obstructive sleep apnoea (OSA) increases with age, yet the risk factors for OSA in older people remain poorly understood. This study aimed to define the age-related changes in upper airway morphology in carefully matched groups of healthy older (>60 years, n=11) and younger (<40 years, n=14) males, using direct (magnetic resonance imaging (MRI)) and indirect (acoustic reflection) imaging. The median (interquartile range) combined retropalatal and retroglossal pharyngeal length was greater in older than in younger males (older 8.8 (7.8-9.0) cm, younger 7.8 (7.0-8.3) cm; p=0.03), as was the soft palate cross-sectional area (older 43.1 (36.0-48.8) cm(2), younger 35.3 (30.5-40.5) cm(2); p=0.03), parapharyngeal fat pad diameter (older 1.7 (1.4-2.2) cm, younger 1.2 (1.0-1.8) cm; p=0.03) and cross-sectional area of the fat pads (older 13.8 (9.1-17.1) cm(2); younger 7.4 (5.9-13.0) cm(2); p=0.02) as measured by MRI. Using acoustic reflection, pharyngeal calibre (older 4.8 (3.8-6.6) cm(2), younger 3.4 (2.8-4.6) cm(2); p=0.03), pharyngeal volume (older 35.1 (30.9-55.4) cm(3), younger 27.2 (22.7-44.2) cm(3); p=0.04) and glottis area (older 2.7 (2.1-3.9) cm(2), younger 1.3 (1.1-1.9) cm(2); p=0.003) were also larger in older participants compared with younger participants. There was no difference in craniofacial measures between groups, including volumetric data and hyoid bone position. The larger pharyngeal calibre observed in older males may be compensating for an age-related enlargement in pharyngeal soft tissue that predisposes to OSA.

CBCT Evaluation of the Upper Airway Morphological Changes in Growing Patients of Class II Division 1 Malocclusion with Mandibular Retrusion Using Twin Block Appliance: A Comparative Research

ObjectiveThe purpose of this study was to evaluate the morphological changes of upper airway after Twin Block (TB) treatment in growing patients with Class II division 1 malocclusion and mandibular retrusion compared with untreated Class II patients by cone beam computed tomography (CBCT).Materials and MethodsThirty growing patients who have completed TB treatment were recruited into TB group. The control group (n = 30) was selected from the patients with the same diagnosis and without TB treatment. CBCT scans of the pre-treatment (T1) and post-treatment (T2) data of TB group and control data were collected. After three-dimensional (3D) reconstruction and registration of T1 and T2 data, the morphological changes of upper airway during TB treatment were measured. The statistical differences between T1 and T2 data of TB group as well as T2 and control data were accessed by t-test.ResultsDuring the TB treatment, the mandible moved advanced by 3.52±2.14 mm in the horizontal direction and 3.77±2.10 mm in the vertical direction. The hyoid bone was in a more forward and inferior place. The upper airway showed a significant enlargement in nasopharynx, oropharynx and hypopharynx. In addition, the nasopharynx turned more circular, and the oropharynx became more elliptic in transverse shape. However, the transverse shape of the hypopharynx showed no significant difference. After comparison between T2 and control data, only the horizontal movement of the hyoid bone, the volumetric expansion of the oropharynx and hypopharynx, and changes of the oropharyngeal transverse shape showed significant difference.ConclusionCompared to the untreated Class II patients, the upper airway of growing patients with Class II division 1 malocclusion and mandibular retrusion showed a significant enlargement in the oropharynx and hypopharynx as well as a more elliptic transverse shape in the oropharynx, and the hyoid bone moved to an anterior position after TB treatment.

Intra-amniotic LPS amplifies hyperoxia-induced airway hyperreactivity in neonatal rats.

Background:We previously showed that intra-amniotic lipopolysaccharide (LPS) amplifies alveolar hypoplasia induced by postnatal hyperoxia. We determined whether the priming effect of intra-amniotic LPS amplifies hyperoxia-induced airway hyperreactivity (AHR).Methods:LPS or normal saline was injected into the amniotic cavities of pregnant rats at the 20th day of gestation. After birth, rat pups were exposed to 60% O2 or air for 14 d. On postnatal day 14, rat pups underwent forced oscillometry, which included a challenge with nebulized methacholine, and the lungs were harvested for morphological studies.Results:Hyperoxia significantly increased airway reactivity and decreased compliance. Intra-amniotic LPS further increased hyperoxia-induced AHR but did not further impair respiratory system compliance. Hyperoxia-induced changes in lung parenchymal and small airway morphology were not further altered by intra-amniotic LPS. However, combined exposure to intra-amniotic LPS and hyperoxia increased the proportion of degranulating mast cells in the hilar airways.Conclusion:Intra-amniotic LPS amplified postnatal hyperoxia-induced AHR. This was associated with increased airway mast cell degranulation, which has previously been linked with hyperoxia-induced AHR. There were no morphologic changes of parenchyma or airways that would account for the LPS augmentation of hyperoxia-induced AHR.

MiR-221 and miR-130a Regulate Lung Airway and Vascular Development

Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin) immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U) were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung.

A randomised titrated crossover study comparing two oral appliances in the treatment for mild to moderate obstructive sleep apnoea/hypopnoea syndrome

The objective of this study was to compare the efficiency of two oral appliances in patients with mild to moderate obstructive sleep apnoea/hypopnoea syndrome (OSAHS) by the analysis of objective and subjective evaluations and measurement of upper airway parameter. A randomised crossover design trial was carried out on 16 patients with OSAHS. Two different types of oral appliances were tested in each patient, a one-piece monoblock and the SILENT NITE(®) (GlideWell Laboratories, Newport Beach, CA, USA), a two-piece appliance. Each oral appliance needed to be worn for two 3-month periods separated by a 2-week wash-out period in between. The objective and subjective efficiency and upper airway parameters associated with the oral appliances were assessed. One-way analysis of variance (anova) test was performed to compare the changes in upper airway morphology and the treatment efficiency between the appliances. The monoblock and SILENT NITE(®) (GlideWell Laboratories) appliances reduced Apnoea Hypopnoea Index (AHI) from 26·38±4·13 to 7·58±2·28 (P<0·001) and 8·87±2·88 (P<0·001), respectively. The monoblock appliance was statistically more efficient in reducing AHI and Apnoea Index (AI) than the SILENT NITE(®) (GlideWell Laboratories) (P<0·05). The scores on Epworth's Sleepiness Scale (ESS) and Snoring Scale (SS) were improved significantly by both appliances. The upper airway spaces showed considerable enlargement by both mandibular advancement appliances (MAAs) (P<0·05), while no significant differences were found between the two appliances (P>0·05). Both MAAs showed good efficacy in the treatment for mild to moderate OSAHS. Use of the monoblock appliance should be considered when patients with OSAHS choose MAA treatment, as it was more efficient in reducing the AHI and AI compared to the two-piece appliance and was preferred by most patients. Long-term efficiency should be evaluated in future prospective studies.

Study of the head and neck position in microlaryngoscopy using magnetic resonance imaging

Several studies have critically analyzed the ideal position for laryngeal exposure during microlaryngoscopy; however, these studies have lacked the ability to evaluate the head and neck position while maintaining a direct view into the airway. Therefore, a newly established two-curve methodology was used to investigate the influence of head and neck position during microlaryngoscopy in MRI images. Fourteen normal adult volunteers were used in this magnetic resonance imaging study. The airway was divided into two curves in the sagittal plane at the center of the airway in three head and neck positions: extension-extension, neutral and flexion-extension position. The airway passage curves, point of inflection and its tangent, the line of laryngoscope, line of hyoid bone and mandible were plotted on each scan. Angles and area formed by these lines were calculated to evaluate the airway morphology changes. The flexion-extension position caused a reduction in the area between the line of laryngoscope and curves, but there was no significant difference between the three positions (p = 0.664). The flexion-extension position also resulted in the lowest angle values for α (angle between the tangent and horizon, p = 0.000), β (between the line of hyoid and horizon, p = 0.002) and δ (between the line of mandible and horizon, p = 0.004). Our study provides a better understanding of the changes in normal airway morphology during microlaryngoscopy in different positions, reinforcing the concept that flexion-extension position is the optimal position for microlaryngoscopy.

Effect of Maxillomandibular Advancement on Morphology of Velopharyngeal Space

The objectives of the present study were to assess the changes in upper airway morphology and function in response to advancement of the maxilla and mandible. Orthognathic surgery was performed. During the surgery, the maxilla and mandible were each advanced as a maxillomandibular advancement simulation. A total of 18 patients with a chief complaint of malocclusion were studied. The distance in jaw advancement and the anteroposterior and left-right diameters of the velopharyngeal space before and after jaw advancement were measured. After the anteroposterior and left-right dilation rates and area enlargement rates were calculated, we compared advancement of the maxilla with that of the mandible. Each of the jaw advancements resulted in statistically significant increases in the anteroposterior and left-right diameters of the velopharyngeal space, and the area was significantly enlarged. The anteroposterior dilation rate was significantly greater after advancement of the maxilla, and the left-right dilation rate was significantly greater after advancement of the mandible. The velopharyngeal space area enlargement rate was significantly greater with advancement of the maxilla. These data suggest that the mode of dilation of the velopharyngeal space differs between maxillary advancement and mandibular advancement. Jaw advancement affects the soft palate muscles, and the velopharyngeal space is expanded 3-dimensionally by each of those muscles. The difference in the pattern of expansion of the velopharyngeal space was related to differences in the functions of the soft palate muscles.

Small airway remodeling in acute respiratory distress syndrome: a study in autopsy lung tissue.

IntroductionAirway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients.MethodsWe retrospectively studied autopsy lung tissue from subjects who died with ARDS and from control subjects who died of non pulmonary causes. Using image analysis, we quantified the extension of epithelial changes (normal, abnormal and denudated epithelium expressed as percentages of the total epithelium length), bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. The Student's t-test or the Mann-Whitney test was used to compare data between the ARDS and control groups. Bonferroni adjustments were used for multiple tests. The association between morphological and clinical data was analyzed by Pearson rank test.ResultsThirty-one ARDS patients (A: PaO2/FiO2 ≤200, 45 ± 14 years, 16 males) and 11 controls (C: 52 ± 16 years, 7 males) were included in the study. ARDS airways showed a shorter extension of normal epithelium (A:32.9 ± 27.2%, C:76.7 ± 32.7%, P < 0.001), a larger extension of epithelium denudation (A:52.6 ± 35.2%, C:21.8 ± 32.1%, P < 0.01), increased airway inflammation (A:1(3), C:0(1), P = 0.03), higher airway wall thickness (A:138.7 ± 54.3 μm, C:86.4 ± 33.3 μm, P < 0.01), and higher airway content of collagen I, fibronectin, versican and matrix metalloproteinase-9 (MMP-9) compared to controls (P ≤0.03). The extension of normal epithelium showed a positive correlation with PaO2/FiO2 (r2 = 0.34; P = 0.02) and a negative correlation with plateau pressure (r2 = 0.27; P = 0.04). The extension of denuded epithelium showed a negative correlation with PaO2/FiO2 (r2 = 0.27; P = 0.04).ConclusionsStructural changes in small airways of patients with ARDS were characterized by epithelial denudation, inflammation and airway wall thickening with ECM remodeling. These changes are likely to contribute to functional airway changes in patients with ARDS.

舌リンパ管腫に起因する開咬症における舌・気道形態の変化

This study examined the long-term changes in tongue and pharyngeal airway morphology of a 7-year-old girl. She had a severe vertical jaw deformity with a 17-mm anterior open bite due to macroglossia. She had already undergone surgical reduction glossectomy two times prior to the initial consultation in our clinic. Tooth extraction and orthognathic surgery were avoided to maintain sufficient oral cavity volume for the large tongue. After 3-year multi-bracket system (MBS) treatment, the malocclusion and masticatory dysfunction were corrected appropriately. Moreover, cephalometric evaluation during the orthodontic treatment showed no morphological disharmony of the tongue and pharyngeal airway. However, the tongue position displaced backward due to the correction of the open bite. In this patient, sleep-disorder breathing as a result of the reduction in size of the pharyngeal airway might occur in the future. Therefore, long-term follow-up observation is required for preventing morphological changes in the pharyngeal airway and relapse due to macroglossia.

呼吸様式の変化に伴う上気道形態の変化―睡眠ファイバーとＭＤＣＴ画像解析による検討―

Several studies have reported that the most effective breathing pattern is nasal breathing during wakefulness and open-mouth breathing induce upper airway narrowing by the morphological changing of the upper airway. The aim of the present study was to conduct an objective investigation of upper airway morphological changes corresponding with changes in breathing patterns using sleep endoscopy and three-dimensional imagery of the upper airway by a volume rendering technique with MDCT images. Result: The endoscopic findings of tongue retreating during wakeful mouth breathing were obtained with both obstructive sleep apnea syndrome (OSAS) patients and a normal control. It was confirmed that the narrowing of the upper airway with OSAS patients worsened. Three-dimensional images of the upper airway by a volume rendering technique with MDCT images was also successful in obtaining findings in changes of breathing patterns using endoscopy. It was very helpful to be able to observe from any angle. Conclusion: These methods have potential in establishing an objective evaluation method, as well as being very useful in providing a visually descriptive explanation to patients.

Cigarette smoke induces CXCL8 production by human neutrophils via activation of TLR9 receptor

Chronic obstructive pulmonary disease (COPD) is a major health problem and cigarette smoke is the main risk factor for the development of COPD. The characteristic changes in airway morphology, inflammatory cell infiltration and mediator expression in COPD may result from direct effects of cigarette smoke on airway cells. Toll-like receptors (TLRs) are key elements in pathogen recognition by the host immune system. Although TLRs have been intensely studied in innate immunity and infection, their critical role in noninfectious challenges has only recently emerged. Here we investigate whether cigarette smoke induces TLR9 signalling in human neutrophils. Human neutrophils were isolated from buffy coat and exposed to cigarette smoke extract. The production of CXC chemokine ligand (CXCL)8 was measured as a functional readout and the role of TLR9 signalling was investigated. Cigarette smoke extract induced CXCL8 release via TLR9 activation in neutrophils, which was confirmed in TLR9 stably transfected human embryonic kidney 293 cells. Moreover, cigarette smoke extract upregulated the expression of TLR9 and the upregulated expression was suppressed by N-acetylcysteine. TLR9 mediates cigarette smoke-induced release of CXCL8 and this may contribute to the accumulation of neutrophils and inflammation within the airways of smokers.

Effects of a mandibular advancement device on the upper airway morphology: a cephalometric analysis

The aims of this study were to assess changes in the upper airway morphology associated with an oral appliance in situ in patients suffering from the obstructive sleep apnoea-hypopnoea syndrome and to relate these changes to treatment response. Changes in upper airway morphology as a result of an oral appliance were assessed in 52 patients with obstructive sleep apnoea-hypopnoea syndrome by means of cephalometric analysis. Lateral cephalograms were taken at baseline and after 2-3 months of treatment. Baseline and follow-up cephalograms were traced twice and cephalometric variables were compared. The predictive value of changes in upper airway morphology for the treatment response was evaluated in univariate and multivariate regression analyses. Oral appliance therapy resulted in an increased posterior airway space at the level of the second vertebra, the uvular tip and the base of the tongue. The increase of the posterior airway space at the level of the second vertebra and the uvular tip were the best predictors for relative improvement of the apnoea-hypopnoea index. However, the predictive value for treatment response of these cephalometric upper airway changes should be interpreted with caution.

Upper airway morphologic changes in obstructive sleep apnea hypopnea syndrome patients before and after orthognathic surgery and distraction osteogenesis

To investigate the morphologic changes of upper airway in obstructive sleep apnea and hypopnea syndrome (OSAHS) associated with micrognathism before and after orthognathic surgery and distraction osteogenesis, and subsequently to instruct clinical jobs effectively. Nine OSAHS patients associated with micrognathism (8 males, 1 female, mean age: 28.6 years) received orthognathic surgery and (or) distraction osteogenesis, and the curative effect was evaluated according to the subjective feelings and PSG. Upper airway structure before and after the treatment was measured by Somatom Sensation 16 CT scanner. All 9 patients were clinically cured. The transverse length, the cross section area, and especially the sagittal length of the upper airway were obviously increased after the orthognathic surgery. The changes involved mainly in the velopharyngeal region and the laryngopharyngeal region, but not in the laryngopharyngeal region. The orthognathic surgery and distraction osteogenesis can treat the OSAHS patients with microgonathism effectively by increasing their velopharyngeal and laryngopharyngeal sagittal length of upper airway.

Acute and chronic responses of the upper airway to inspiratory loading in healthy awake humans: An MRI study

We assessed upper airway responses to acute and chronic inspiratory loading. In Experiment I, 11 healthy subjects underwent T(2)-weighted magnetic resonance imaging (MRI) of upper airway dilator muscles (genioglossus and geniohyoid) before and up to 10 min after a single bout of pressure threshold inspiratory muscle training (IMT) at 60% maximal inspiratory mouth pressure (MIP). T(2) values for genioglossus and geniohyoid were increased versus control (p<0.001), suggesting that these airway dilator muscles are activated in response to acute IMT. In Experiment II, nine subjects underwent 2D-Flash sequence MRI of the upper airway during quiet breathing and while performing single inspirations against resistive loads (10%, 30% and 50% MIP); this procedure was repeated after 6 weeks of IMT. Lateral narrowing of the upper airway occurred at all loads, whilst anteroposterior narrowing occurred at the level of the laryngopharynx at loads > or =30% MIP. Changes in upper airway morphology and narrowing after IMT were undetectable using MRI.

Surgical treatment for sleep apnea: changes in craniofacial and pharyngeal airway morphology in a child with achondroplasia

Here, we report the case of a male child with achondroplasia who was diagnosed with obstructive sleep apnea and underwent adenoidectomy and tonsillectomy. By analyzing lateral cephalograms, we evaluated the craniofacial and pharyngeal airway morphology immediately before surgery (age, 5 years 6 months) and 1 year 2 months after surgery (age, 6 years 8 months). Adenoidectomy and tonsillectomy dilated the pharynx and improved the craniofacial and pharyngeal morphologies, apparently thus improving the sleep apnea.

Airway Mucosal Thickening and Bronchial Hyperresponsiveness Induced by Inhaled β2-Agonist in Mice

Patients with chronic persistent asthma require frequent use of inhaled beta(2)-agonist, which may result in aggravation of asthma symptoms. Our recent in vitro study has shown that beta(2)-agonist stimulates the growth of human airway epithelial cell lines. To determine whether beta(2)-agonist likewise affects airway epithelial cell proliferation in vivo and, if so, what the mechanism of action is, we examined the effect of salbutamol on the morphology of murine airways. Seventy-two BALB/c mice were administered aerosolized salbutamol using "flow-through" nose-only inhalation chambers at daily doses of 0.2 to 20 microg for up to 6 weeks. Morphology of tracheal mucosa, labeling of epithelial cells with 5-bromo-2'-deoxyuridine (BrdU), and bronchial responsiveness were assessed. Exposure to salbutamol increased the thickness of tracheal epithelial layer and the number of BrdU-positive epithelial cells in a dose- and time-dependent manner: the values in mice receiving 20 microg salbutamol for 6 weeks were 247% and 642%, respectively, of those in control animals receiving saline solution alone. These effects were inhibited by the mitogen-activated protein (MAP) kinase kinase inhibitors PD98059 and U0126. Salbutamol also caused a decrease in the provocative concentration of methacholine to achieve 400% of baseline enhanced pause. Combined treatment with inhaled budesonide attenuated salbutamol-induced airway morphologic changes and bronchial hyperresponsiveness. beta(2)-agonist stimulates proliferation of airway epithelial cells and produces airway wall thickening in vivo via MAP kinase-dependent pathway, and these effects are prevented by inhaled corticosteroid.

Long-term changes in pharyngeal airway morphology after mandibular setback surgery

Long-term changes in pharyngeal airway morphology were evaluated after mandibular setback surgery in 10 women who were diagnosed as having skeletal mandibular prognathism and underwent mandibular setback surgery by bilateral sagittal split ramus osteotomy (SSRO) and orthodontic multi-bracket treatment. The subjects were assessed before treatment (T1), 3-6 months after SSRO (T2), and 2 or more years after SSRO (T3). From T1 to T2, the pharyngeal airway constricted significantly. On the other hand, from T2 to T3, the lower facial morphology showed no significant changes. The pharyngeal airway morphology showed significant changes in soft-palate length and posterior reference line to point of posterior tongue, indicating a tendency for relapse. These results suggest that, although the lower facial morphology and the pharyngeal airway morphology showed marked changes after SSRO, the pharyngeal airway morphology exhibited gradual physiologic readaptation. However, because the lower facial morphology after surgery was retained and stable for a long period, it was considered normal for the pharyngeal airway morphology to adapt after surgery to the improved hard tissue relationship.