["Somatic symptom disorders" in adolescence. A systematic review of the recent literature]. / « Troubles à symptomatologie somatique ¼ chez les adolescents. Une revue systématique.

OBJECTIVES: Body expression of mental disorders is common in adolescence. Only two literature reviews over the last five years have been identified about somatoform disorders in children., The present article provides a systematic review of articles in English, which concern "Somatic Symptom and Related Disorders" according to the DSM-5 (Diagnostic and Statistical Manual - 5th Edition) among adolescents. METHODS: The article search was made on Medline, Psychinfo, Google Scholar, BiomedCentral, Central and tripdatabase (for grey literature) according to PRISMA criteria and with the items "somatoform disorders" or "somatic symptom disorders". An age filter was applied for "adolescents", and a selection was done from the last five years. All articles concerning adolescents (often associated with children) were initially included, except for articles concerning eating disorders, dysmorphic disorders or adult population. Comments, editorials, opinion or descriptive articles were also excluded. The authors then carried out an analysis of the main topics, themes and questions covered in the selected publications and presented a descriptive synthesis. RESULTS: A total of seventy-seven publications were included in the analysis, from three hundred and seventy-two publications. First, the terms used to refer to these "somatic symptom disorders" were varied, such as "somatization", "somatic complaints/symptoms", "functional disorder", "unexplained symptoms" and "somatoform disorders". Then, studies related just to adolescents were limited: most of studies included children and adolescents in their methodologies; and some of them questioned somatic symptoms from a developmental perspective. Case reports were the most represented articles among all medical specialties, with clinical descriptions about "functional neurological symptom disorder", "factitious disorder" and "somatic symptom disorder" with a medical disease, among children and adolescents. We sometimes observed a controversial borderline between psychological and somatic disorders. Various explanatory models appeared, especially the trauma path; familial and social environment was also pointed out, with a possible peer group effect; neurocognitive theories were finally described. The literature highlights the effectiveness of psychosocial therapies (especially the cognitive-behavioral therapy) and the importance of multidisciplinary management. Finally, a few studies with a qualitative methodology are represented. CONCLUSIONS: Only nine articles included "somatic symptom disorder" in their titles, despite a terminology valued by many authors (compared to "somatoform disorders" from the DSM-IV). The heterogeneity of terminologies, case reports and explanatory models witness a lack of connexions between medical specialties. This could explain in part the wandering of adolescents and their families in the health care system. It could also contribute to the delay before diagnosis, especially when neurological symptoms exist, and a late referral for psychiatric consultation. Further studies are needed to understand difficulties to use a clinical pathway among medical specialties, when the benefit of amultidisciplinary approach seems to be unanimous.

The semi-seated position slightly reduces the effort to breathe during difficult weaning.

PURPOSE: The influence of posture on breathing effort in patients with difficult weaning is unknown. We hypothesized that posture could modulate the breathing effort in difficult-to-wean patients. METHODS: A prospective, crossover, physiologic study was performed in 24 intubated patients breathing with pressure support who had already failed a spontaneous breathing trial or an extubation episode. Their median duration of mechanical ventilation before measurements was 25 days. Breathing pattern, occlusion pressure (P (0.1)), intrinsic PEEP (PEEP(i)), and inspiratory muscle effort evaluated by the pressure-time product of the respiratory muscles and the work of breathing were measured during three postures: the seated position in bed (90°LD), simulating the position in a chair, the semi-seated (45°), and the supine (0°) positions consecutively applied in a random order. A comfort score was obtained in 17 cooperative patients. The influence of position on chest wall compliance was measured in another group of 11 sedated patients. RESULTS: The 45° position was associated with the lowest levels of effort (p ≤ 0.01) and occlusion pressure (p < 0.05), and tended to be more often comfortable. Respiratory effort was the lowest at 45° in 18/24 patients. PEEP(i) and PEEP(i)-related work were slightly higher in the supine position (p ≤ 0.01), whereas respiratory effort, heart rate, and P (0.1) values were increased in the seated position (p < 0.05). CONCLUSION: A 45° position helps to unload the respiratory muscles, moderately reduces PEEP(i), and is often considered as comfortable. The semi-seated position may help the weaning process in ventilator-dependent patients.

[Externalizing behaviour problems of internationally adopted adolescents: a review]. / Troubles du comportement externalisés à l'adolescence et adoptions internationales: revue de la littérature.

INTRODUCTION: International adoption involves more than 40 000 children a year. The objective of this review is to estimate the effects of international adoption on externalizing behaviour problems during adolescence. In this paper we examine the prevalence of externalizing problem behaviours in samples of adolescents who were adopted from a foreign country as infants or young children, compare to non-adopted adolescents. SETTING: We searched Medline, Inist and psycInfo from 1960 to 2005 using the terms adopt* combined with behaviour problem, behaviour disorder, maladjustment or mental health. METHODS: The search was limited to English and French-language publications. Studies that were selected involved adoptees in the general population and compared international adoptees with non-adopted controls. Adoptees from 12 to 22 years old were included. We included studies using the Child Behaviour Check List or related measures to measure externalizing problem behaviour. We reviewed 10 studies from 1990 to 2002 and 2 meta-analyses (2003, 2005). RESULTS: Results indicate that 6 studies conclude that internationally adopted adolescents exhibit more externalizing behaviour problems than do non-adopted adolescents, and 4 studies conclude that there is no difference between the two groups. The two meta-analyses concluded that the prevalence of externalizing behaviour problems is increased. The difference, however, is small. International adoptees with preadoption adversity showed more externalizing problems than international adoptees whithout evidence of extreme deprivation. CONCLUSION: Finally, it should be stressed that adoption itself is not a risk factor in the adjustment of adolescents. Differences between groups of adopted and non-adopted adolescents may reflect the presence of a small number of severely disturbed adolescents, possibly with extremely adverse pre-placement histories.

Transforming growth factor-beta1 increases airway wound repair via MMP-2 upregulation: a new pathway for epithelial wound repair?

In vivo, transforming growth factor (TGF)-beta1 and matrix metalloproteinases (MMPs) present at the site of airway injury are thought to contribute to epithelial wound repair. As TGF-beta1 can modulate MMP expression and MMPs play an important role in wound repair, we hypothesized that TGF-beta1 may enhance airway epithelial repair via MMPs secreted by epithelial cells. We evaluated the in vitro influence of TGF-beta1 on wound repair in human airway epithelial cells cultured under conditions allowing differentiation. The results showed that TGF-beta1 accelerated in vitro airway wound repair, whereas MMP inhibitors prevented this acceleration. In parallel, we examined the effect of TGF-beta1 on the expression of MMP-2 and MMP-9. TGF-beta1 induced a dramatic increase of MMP-2 expression with an increased steady-state level of MMP-2 mRNA, contrasting with a slight increase in MMP-9 expression. To confirm the role of MMP-2, we subsequently evaluated the effect of MMP-2 on in vitro airway wound repair and demonstrated that the addition of MMP-2 reproduced the acceleration of wound repair induced by TGF-beta1. These results strongly suggest that TGF-beta1 increases in vitro airway wound repair via MMP-2 upregulation. It also raises the issue of a different in vivo biological role of MMP-2 and MMP-9 depending on the cytokine microenvironment.

Induction of type-IIA secretory phospholipase A2 in animal models of acute lung injury.

The aim of this study was to evaluate the presence of type-II secretory phospholipase A2 (sPLA2-IIA) in alveolar space and its possible role in the destruction of surfactant in three rat models of acute lung injury. Alveolar instillation of either lipopolysaccaride or live Pseudomonas aeruginosa resulted in a significant increase in lung oedema and in a decrease in static compliance of the respiratory system together with alveolar-neutrophil influx as compared with healthy control rats. The upregulation of messenger ribonucleic acid and sPLA2-IIA by the lung was evident. This was associated with surfactant degradation and a decrease in large:small ratio of surfactant aggregates in bacteria-instilled rats. A negative correlation between compliance and sPLA2-IIA activity in bronchoalveolar lavage fluid was shown. By contrast, during alpha naphthylthiourea-induced injury, neither alveolar-neutrophil influx nor increase in sPLA2-IIA activity was observed. Additional experiments in rats treated with a specific inhibitor of type-II secretory phospholipase A2 activity (3 acetamine-1-benzyl-2 ethylindolyl-5 oxy; propane phosphonic acid (LY311727)) demonstrated no improvement in physiological parameters despite a biochemical effect, suggesting that its activity is only one of the multiple factors involved in the pathophysiology of lung injury.

Bench testing of pressure support ventilation with three different generations of ventilators.

OBJECTIVE: The new generations of intensive care ventilators tend to be more innovative and sophisticated than previous ones, but little is known about their respective performance for delivering pressure support ventilation (PSV) and how they compare to previous generations. DESIGN: Active lung model bench test. APPARATUS: Twenty-two commercially available ventilators classified into three categories: new generation ventilators (after 1993, n=7), previous generation (before 1993, n=6), and recent piston or turbine-based ventilators ( n=9). MEASUREMENTS AND RESULTS: During PSV, the unloading efficacy of the assistance depends on the ventilator's ability to meet inspiratory flow demand. Three levels of flow (0.1 l/s, 0.6 l/s, and 1.2 l/s) were used to simulate inspiratory demand and the net area of the inspiratory airway pressure-time trace was calculated over the first 0.3 s, 0.5 s, and 1 s (Area (0.3), Area (0.5), and Area (tot)) with three levels of PSV (5 cmH(2)O, 10 cmH(2)O, and 15 cmH(2)O). To assess the respective role of pressure support delivery and triggering function, triggering sensitivity was assessed independently by measuring the time delay ( TD (tg)) and the pressure fall (Delta Paw (tg)) with two levels of inspiratory drive. All the new generation ventilators exhibited significantly better results than most of the previous generation ventilators regarding Area (0.3) and TD (tg), indicating large improvements in terms of triggering and pressurisation. CONCLUSION: Regarding PSV and trigger performance, the new generation ventilators - but also some piston and turbine-based ventilators - outperform most of previous generation ventilators.

Segmental analysis of nasal cavity compliance by acoustic rhinometry.

To explore the determinants of possible collapse of the nasal valve region, a common cause of nasal obstruction, we evaluated the mechanical properties of the nasal wall. In this study, we determined the nasal cross-sectional area-to-negative pressure ratio (nasal wall compliance) in the anterior part of the nose in six healthy subjects by measuring nasal area by acoustic rhinometry at pressures ranging from atmospheric pressure to a negative pressure of -10 cmH(2)O. Measurements were performed at baseline and after nasal mucosal decongestion (oxymetazoline). At baseline, nasal wall compliance increased progressively from the nasal valve (0.031 +/- 0.016 cm2/cmH(2)O, mean +/- SD) to the anterior and medial part of the inferior turbinate (0.045 +/- 0.024 cm2/cmH(2)O) and to the middle meatus region (0.056 +/- 0.029 cm2/cmH(2)O). After decongestant, compliances decreased and became similar in the three regions. On the basis of these results, we hypothesize that compliance of the nasal wall is partly related to mucosal blood volume and quantity of vascular tissue, which differ in the three regions, increasing from the nasal valve to the middle meatus.

Use of glass capillaries avoids the time changes in high blood PO(2) observed with plastic syringes.

STUDY OBJECTIVES: In adults, arterial blood samples are usually drawn using plastic syringes. In contrast to glass syringes, plastic syringes let oxygen diffuse through their wall. This results in PO(2) changes during storage, especially when PO(2) is high. An alternative to glass syringes is the Microsampler (Roche Diagnostics; Schaffhausen, Switzerland), a commercially available device consisting of a heparinized glass capillary fitted with a 26-gauge needle and used to collect arterial blood in the same way as a plastic syringe fitted with a needle. DESIGN: We evaluated the performance of the Roche Microsampler for storing arterial blood in view of PO(2) measurement, comparatively with glass and plastic syringes. Five approximate initial PO(2) levels (650, 400, 200, 130, and 80 mm Hg) and two storage temperatures (ambient temperature and 4 degrees C) were studied. SETTINGS: Bench study. RESULTS: Plastic syringes allowed reliable measurement of PO(2) values when initial PO(2) was too low to ensure complete hemoglobin oxygen saturation, but were associated with time-dependent underestimation of PO(2) at higher initial PO(2) values. No such underestimation occurred with the Roche Microsampler stored at 4 degrees C for up to 1 h for all PO(2) levels studied. CONCLUSION: The Roche Microsamplers appeared to be reliable devices in preventing oxygen diffusion.

Comparison of the forced oscillation technique and the interrupter technique for assessing airway obstruction and its reversibility in children.

The forced oscillation technique (FOT) and interrupter technique are particularly attractive for pediatric use as they require only passive cooperation from the patient. We compared the sensitivity and specificity of these methods for detecting airway obstruction and its reversibility in 118 children (3-16 yr) with asthma or chronic nocturnal cough. FOT (R(0) and R(16)) and interruption (Rint) parameters were measured at baseline and after bronchodilator inhalation (n = 94). Rint was significantly lower than R(0), especially in children with high baseline values. Baseline parameters were normalized for height and weight [R(SD)]. In children able to perform forced expiratory maneuvers (n = 93), the best discrimination between those with baseline FEV(1) < 80% or > or = 80% of predicted values was obtained with R(0)(SD). At a specificity of 80%, R(0)(SD) yielded 66% sensitivity, whereas Rint(SD) yielded only 33% sensitivity. Similarly, postbronchodilator changes in R(0)(SD) [DeltaR(0)(SD)] yielded the best discrimination between children with and without significant reversibility in FEV(1). At a specificity of 80%, DeltaR(0)(SD) yielded 67% sensitivity and DeltaRint(SD) yielded 58% sensitivity. In children unable to perform forced expiratory maneuvers (n = 25), FOT, contrary to the interrupter technique, clearly identified a subgroup of young children with high resistance values at baseline, which returned to normal after bronchodilation. We conclude that, in asthmatic children over 3 yr old, FOT measurements provide a more reliable evaluation of bronchial obstruction and its reversibility compared with the interrupter technique, especially in young children with high baseline values.

Accuracy of pulse oximetry in the intensive care unit.

OBJECTIVE: Pulse oximetry (SpO2) is a standard monitoring device in intensive care units (ICUs), currently used to guide therapeutic interventions. Few studies have evaluated the accuracy of SpO2 in critically ill patients. Our objective was to compare pulse oximetry with arterial oxygen saturation (SaO2) in such patients, and to examine the effect of several factors on this relationship. DESIGN: Observational prospective study. SETTING: A 26-bed medical ICU in a university hospital. PATIENTS: One hundred two consecutive patients admitted to the ICU in whom one or serial arterial blood gas analyses (ABGs) were performed and a reliable pulse oximeter signal was present. INTERVENTIONS: For each ABG, we collected SaO2, SpO2, the type of pulse oximeter, the mode of ventilation and requirement for vasoactive drugs. MEASUREMENTS AND RESULTS: Three hundred twenty-three data points were collected. The mean difference between SpO2 and SaO2 was -0.02% and standard deviation of the differences was 2.1%. From one sample to another, the fluctuations in SpO2 to arterial saturation difference indicated that SaO2 could not be reliably predicted from SpO2 after a single ABG. Subgroup analysis showed that the accuracy of SpO2 appeared to be influenced by the type of oximeter, the presence of hypoxemia and the requirement for vasoactive drugs. Finally, high SpO2 thresholds were necessary to detect significant hypoxemia with good sensitivity. CONCLUSION: Large SpO2 to SaO2 differences may occur in critically ill patients with poor reproducibility of SpO2. A SpO2 above 94% appears necessary to ensure a SaO2 of 90%.

Abdominal muscle activity in sleep apnea during continuous positive airway pressure titration.

STUDY OBJECTIVES: The aim of this study was to investigate whether presence of expiratory abdominal muscle activity (EAMA) in obstructive sleep apnea syndrome (OSAS) patients during nasal continuous positive airway pressure (nCPAP) is due to either nCPAP overprescription or nCPAP underprescription. DESIGN: Airflow, esophageal pressure (Pes), and gastric pressure (Pga) were routinely measured during polysomnography aimed at determining the optimal nCPAP level, and the magnitude of EAMA was evaluated in relation to the nCPAP level and to the conventional indexes of upper-airway obstruction used during nCPAP titration. PATIENTS: The study was performed 12 patients with OSAS. RESULTS: Six patients displayed sustained EAMA, ie, EAMA lasting > 3 min, and characterized by a decrease in abdominal diameter and a paradoxical rise in Pga during expiration. In all six patients, EAMA decreased gradually as nCPAP neared optimal levels, and then disappeared when the optimal nCPAP level was achieved. The decrease in EAMA as nCPAP increased was associated with an increase in minute ventilation, decreases in both inspiratory and expiratory resistance, a decrease in Pes swing, and the normalization of the inspiratory flow contour. CONCLUSIONS: We conclude that the EAMA observed in some OSAS patients might be an indirect marker of upper-airway obstruction, and that the presence of EAMA during nCPAP titration might indicate a suboptimal nCPAP level rather than a deleterious effect of nCPAP.

Helium-oxygen in the postextubation period decreases inspiratory effort.

After tracheal extubation, upper and total airway resistances may frequently be increased resulting in an increase in inspiratory effort to breathe. We tested whether breathing a helium-oxygen mixture (HeO(2)) would reduce inspiratory effort in the period after extubation. Eighteen consecutive patients with no chronic obstructive pulmonary disease who had received mechanical ventilation (> 48 h) were successively studied immediately after extubation (N(2)O(2)), 15 min after breathing HeO(2), and after return to N(2)O(2). Effort to breathe, assessed by the transdiaphragmatic pressure swings (DeltaPdi) and the pressure-time index of the diaphragm (PTI), comfort, and gas exchange, were the main end points. The mean reduction of the transdiaphragmatic pressure under HeO(2) was 19 +/- 5%. All but three patients presented a decrease in transdiaphragmatic pressure under HeO(2), ranging from - 4 to - 55%, and a significant reduction in DeltaPdi was observed between HeO(2) and N(2)O(2) (10.2 +/- 0.7 versus 8.6 +/- 1.1 versus 10.0 +/- 0.8 cm H(2)O for the three consecutive periods; p < 0.05). PTI also differed significantly between HeO(2) and N(2)O(2) (197 +/- 19 versus 166 +/- 22 versus 201 +/- 23 cm H(2)O/s/min for the three periods; p < 0.05). Breathing HeO(2) significantly improved comfort, whereas gas exchange was not modified. We conclude that the use of HeO(2) in the immediate postextubation period decreases inspiratory effort and improves comfort.

Evaluation of basement membrane degradation during TNF-alpha-induced increase in epithelial permeability.

We evaluated whether tumor necrosis factor (TNF)-alpha induces an increase in permeability of an alveolar epithelial monolayer via gelatinase secretion and basement membrane degradation. Gelatinase secretion and epithelial permeability to radiolabeled albumin under unstimulated and TNF-alpha-stimulated conditions of an A549 human epithelial cell line were evaluated in vitro. TNF-alpha induced both upregulation of a 92-kDa gelatinolytic activity (pro form in cell supernatant and activated form in extracellular matrix) and an increase in the epithelial permeability coefficient compared with the unstimulated condition (control: 1.34 +/- 0.04 x 10(-6) cm/s; 1 microg/ml TNF-alpha: 1.47 +/- 0.05 x 10(-6) cm/s, P < 0.05). The permeability increase in the TNF-alpha-stimulated condition involved both paracellular permeability, with gap formation visualized by actin cytoskeleton staining, and basement membrane permeability, with an increase in the basement membrane permeability coefficient (determined after cell removal; control: 2.58 +/- 0.07 x 10(-6) cm/s; 1 microg/ml TNF-alpha: 2.82 +/- 0.02.10(-6) x cm/s, P < 0.05). Because addition of gelatinase inhibitors [tissue inhibitor of metalloproteinase (TIMP)-1 or BB-3103] to cell supernatants failed to inhibit the permeability increase, the gelatinase-inhibitor balance in the cellular microenvironment was further evaluated by cell culture on a radiolabeled collagen matrix. In the unstimulated condition, spontaneous collagenolytic activity inhibited by addition to the matrix of 1 microg/ml TIMP-1 or 10(-6) M BB-3103 was found. TNF-alpha failed to increase this collagenolytic activity because it was associated with dose-dependent upregulation of TIMP-1 secretion by alveolar epithelial cells. In conclusion, induction by TNF-alpha of upregulation of both the 92-kDa gelatinase and its inhibitor TIMP-1 results in maintenance of the gelatinase-inhibitor balance, indicating that basement membrane degradation does not mediate the TNF-alpha-induced increase in alveolar epithelial monolayer permeability.

Radiofrequency is a safe and effective treatment of turbinate hypertrophy.

OBJECTIVE: To evaluate the safety and efficacy of radiofrequency for reduction of inferior turbinate volume. STUDY DESIGN: Prospective before-and-after trial. METHODS: Fourteen patients complaining of chronic nasal obstruction and failing to respond to medical treatment were prospectively enrolled. All patients presented with inferior turbinate hypertrophy and no septal deformity. Radiofrequency inferior turbinate tissue reduction with three punctures in each turbinate (mean energy/puncture: 342 +/- 36 J, mean duration: 69 +/- 17 s, plateau tissue temperature: 75 +/- 6.4 degrees C). Patients were evaluated before and on days 3, 7, and 60 after intervention. RESULTS: No postoperative pain or complications were reported. Evaluation of nasal obstruction, quantified by visual analogue scale, showed a significant decrease of day time and nighttime obstruction after surgery. Acoustic rhinometry measurements showed that turbinate hypertrophy was significantly reduced in the sitting and supine positions on day 60 after surgery. Saccharin transit times decreased significantly on day 60 compared with preoperative measurements. Ciliary beat frequency, measured in vitro in nasal epithelial cells sampled from the inferior turbinate by brushing, was not significantly different before surgery and on day 60 after surgery. In the same samples, ciliated cells were the most abundant epithelial cell type before and after surgery, although in five cases, moderate numbers of squamous cells were detected on either day 7 or day 60 after surgery. CONCLUSION: Radiofrequency is a safe surgical procedure capable of reducing turbinate volume without altering the nasal mucosa, and causing minimal discomfort for the patient.

Respiratory impedance response to continuous negative airway pressure in awake controls and OSAS.

The aim of the study was to determine whether the response of respiratory impedance (Zrs) to decreasing levels of continuous negative airway pressure (CNAP) during wakefulness, differs in controls and subjects with obstructive sleep apnoea syndrome (OSAS). Zrs was measured by the forced oscillation technique (4-32 Hz) in 15 controls and 21 patients with OSAS (apnoea/hypopnoea index >20 per sleep hour) with normal lung function, in the basal state and with application of decreasing CNAP of -5, -10, and -15 hPa. Respiratory resistance was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression analysis of respiratory resistive impedance versus frequency. Respiratory elastance (Ers) and inertance (Irs) were estimated by multilinear regression analysis of respiratory reactance versus frequency, and resonance frequency (RF) was determined as RF=(1/2pi)(Ers/Irs)0.5. In both groups, R0, R16, Ers and RF significantly increased as the CNAP level decreased (p <0.0001 for all). R0, Ers, and RF increased significantly more in OSAS than in controls (p < 0.01, 0.001, and 0.0001, respectively), independently of the severity of obesity. Receiver operator characteristic curves showed that the parameter which best detected OSAS was RF, with a sensitivity of 81% and 93% specificity for the 13.6 Hz cut-off point. The results of the present study suggest that the response of respiratory impedance to decreasing continuous negative airway pressure levels, might allow detection of obstructive sleep apnoea syndrome in subjects with normal lung function.

Plethysmography for the assessment of pneumococcal pneumonia and passive immunotherapy in a mouse model.

The increasing prevalence of resistance to antibiotics of Streptococcus pneumoniae, the main causative agent of community-acquired bacterial pneumonia, necessitates the development of both new therapeutic strategies and noninvasive methods in order to evaluate their efficacy. The efficacy of passive immunotherapy with human intravenous immunoglobulin (IVIG) or solvent alone, administered intranasally or intravenously, was evaluated in a mouse model of acute pneumonia. Lung bacterial load was also evaluated, using a classical but invasive method, as was respiratory function (minute ventilation, respiratory frequency and tidal volume) using plethysmography, a simple noninvasive method commonly used in inhalation toxicology, but not previously used to assess respiratory infection. Forty-eight hours after infectious challenge, the lung bacterial load was significantly lower in IVIG-treated mice than in untreated mice. At the same time, minute ventilation was significantly lower than reference values for untreated mice (36+/-3 versus 57+/-8 mL.min(-1), p<0.01, and 31+/-2 versus 50+/-5 mL.min(-1), p<0.01 for intranasal and intravenous administration of solvent, respectively) but not in mice treated with IVIG by either route of administration. Plethysmography therefore appears to be a simple and reliable test for the follow-up of acute respiratory infection.

Increased expression of matrix metalloproteinase-9 in nasal polyps.

To investigate the role of gelatinases in nasal polyposis, a common and disabling airway disease characterized by chronic inflammation and tissue remodelling, matrix metalloproteinase-2 (MMP-2) and MMP-9 expression was investigated in the nasal polyps (NP) of 24 patients undergoing ethmoidectomy and compared with 15 control nasal mucosal (CM) samples obtained from snorers during turbinectomy. Tissue samples were either frozen for enzymatic analysis or paraffin wax-embedded for immunohistochemistry. Zymography and quantitative image analysis showed that MMP-9 active forms were significantly increased (p<0.05) in NPs compared to CM (44 +/- 40 versus 13 +/- 19x10(3) AU/10 microg protein), while MMP-2 expression was similar in both tissues. Concomitant studies of gelatinase immunoexpression showed that MMP-9 expression was enhanced (4- to 16-fold) in surface epithelium, glands (p<0.05), and submucosal inflammatory cells (p<0.05). In addition, MMP-9 positivity was markedly increased in endothelial cells (p<0.01). In situ zymography demonstrated marked gelatinolytic activity, consistent with the immunolocalization of MMP-2 and MMP-9. These results suggest up-regulation of active MMP-9 in the glands and vessels characteristic of NPs. It is concluded that MMP-9 may play a role in the upper airway remodelling observed during nasal polyposis.

Gelatinase expression in pulmonary arteries during experimental pulmonary hypertension.

Structural remodelling of pulmonary vessels is an important feature of pulmonary hypertension (PH), which reflects distal artery muscularization and matrix remodelling. The matrix metalloproteinases (MMPs) are involved in extracellular matrix turnover and hence, in smooth muscle cell migration and endothelial cell migration and proliferation. Among the MMPs, gelatinases (MMP-2 and MMP-9) can degrade basement membrane components and promote cell proliferation and migration. This study evaluated gelatinases in pulmonary vessels during progressive PH in two rat models: exposure to hypoxia or monocrotaline. Zymography of tissue homogenates revealed an association of progression of hypoxic PH with a time-dependent increase in gelatinase MMP-2 activity, specific to pulmonary vessels. Increased MMP-2 activity was also found 30 days postmonocrotaline. Reverse transcription polymerase chain reaction demonstrated upregulation of MMP-2 messenger ribonucleic acid. Immunolocalization showed MMP-2 throughout the pulmonary vasculature, from the trunk to the distal vessels, with strong staining of the intima, media and adventitia. MMP-2 was found in its active form and gelatinolytic activity was correlated to PH severity. Activity localization by in situ zymography corroborated with the immunolocalization findings. In conclusion, the authors demonstrated that matrix metalloproteinase-2 activity is increased in pulmonary vessels during progression of pulmonary hypertension, probably as a result of involvement in the matrix turnover associated with vascular remodelling during pulmonary hypertension.

Nasal obstruction as a risk factor for sleep apnoea syndrome.

Nasal obstruction has frequently been mentioned as a possible risk factor in obstructive sleep apnoea syndrome (OSAS). Over a 2-yr period, 541 unselected consecutive snorers referred for suspected breathing disorders during sleep were included to undergo posterior rhinomanometry. In addition cephalometric landmarks and body mass index (BMI) were obtained. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. OSAS was defined as 15 episodes, or more, of apnoea or hypopnoea per hour of sleep (AHI). Of the 541 consecutive snorers 528 underwent nasal resistance measurement by posterior rhinomanometry (failure rate: 2.4%). Patients with OSAS (259 patients) had higher nasal resistance than patients without OSAS (2.6+/-1.6 hPa x L x s(-1) versus 2.2+/-1.0 hPa x L x s(-1), respectively, p<0.005). A stepwise multiple regression analysis showed that BMI, male sex, nasal resistance, and cephalometric parameters were contributing factors to the AHI. The r2-value of the multiple regression analysis was 0.183. Nasal resistance contributed 2.3% of the variance (p<0.0001), whereas mandibular plane-hyoid distance, BMI, male sex and age contributed 6.2%, 4.6%, 3% and 1.3% of the variance, respectively. To conclude, daytime nasal obstruction is an independent risk factor for OSAS.