Quantified tracheobronchomalacia disorders and their clinical profiles in children

BACKGROUND: Tracheobronchomalacia (TBM) disorders in children have never been studied using quantified measurements and validated clinical outcome measures. The objectives of the study were to prospectively examine the relationship between malacia lesions and their respiratory illness profiles. METHODS: The site of malacia lesions (eg, tracheomalacia, TBM, and bronchomalacia) were determined, measured, and related to the respective cricoid (ie, airway/cricoid ratio) using the color histogram mode technique. These children and normal control subjects were followed up for 12 months with their respiratory illness profiles determined using the Canadian Acute Respiratory Illness Scale (CARIFS) and cough diary scores. MEASUREMENTS: Outcome measures were respiratory illness frequency (> 12 months), severity score (day-1 CARIFS score), and significant cough interfering with daily activity (score of >or= 3) and illness resolution (time to return to a quarter of CARIFS day 1 score). RESULTS: The group of 116 children were composed of patients with malacia (n = 81) and control subjects (n = 35). The median age of the group was 2.1 years (age range, 0.2 to 17.3 years). The adjusted relative risk of illness frequency was 2.1 (95% confidence interval [CI], 1.3 to 3.4), and of significant cough was 7.2 (95% CI, 1.01 to 27.22) for the malacia group while CARIFS day 1 score was 1.66 (95% CI, 1.1 to 2.56) compared to control subjects. Illness resolution rates at day 14 in the malacia group trended 25% slower than those for control subjects. Malacia type and severity of lesions were not associated with increased rates of illness or worse clinical profiles. CONCLUSION: Children with malacia have an increased likelihood of respiratory illness frequency, severity, significant cough, and tendency for delayed recovery. However, neither the site nor the severity of malacia exhibited any significant dose effect on respiratory illness profiles.     

Surfactant in airway disease

Beta(2)-adrenergic agonists cause a release of pulmonary surfactant into lung airways. The surfactant phospholipids maintain the patency of the conducting airways, but this function is inhibited by plasma proteins entering an inflamed airway. The physical behavior of the surfactant can be studied with a pulsating bubble surfactometer and a capillary surfactometer. Calf lung surfactant extract was found to be inhibited by plasma proteins and by a lowering of temperature. Severe breathing difficulties and malfunctioning surfactant developed in BALB/c mice inhaling ozone or infected with respiratory syncytial virus, mainly as a result of proteins invading the airways. Patients with asthma were challenged with allergens in an area of one lung. BAL fluid (BALF) from such an area contained a surfactant that functioned poorly (ie, an inability to maintain airway openness) compared with BALF from the other lung or from the lungs of healthy volunteers. When proteins in the BALF were removed, surfactant performance clearly improved. Eosinophils, so prominent in asthmatic patients, synthesize the enzyme lysophospholipase, which, together with the enzyme phospholipase A(2), catalyzes the hydrolysis of the main component of the surfactant, phosphatidylcholine. Such hydrolysis incapacitates the ability of the surfactant to maintain airway patency. The treatment of asthma with beta(2)-adrenergic agonists and steroids will have a valuable effect on the surfactant system. It will cause a release of fresh surfactant into terminal airways. Surfactant can also be nebulized and inhaled, which has been shown to be an effective treatment.     

Treatment adherence and outcomes in flexible vs standard continuous positive airway pressure therapy

STUDY OBJECTIVES: To compare adherence and clinical outcomes between flexible positive airway pressure (PAP) [C-Flex; Respironics; Murraysville, PA] and standard PAP therapy (ie, continuous positive airway pressure [CPAP]). DESIGN AND SETTING: A controlled clinical trial of CPAP therapy vs therapy using the C-Flex device in participants with moderate-to-severe obstructive sleep apnea. Participants were recruited from and followed up through an academic sleep disorders center. PARTICIPANTS: Eighty-nine participants were recruited into the study after they had undergone complete in-laboratory polysomnography and before initiating therapy. Participants received either therapy with CPAP (n = 41) or with the C-Flex device (n = 48), depending on the available treatment at the time of recruitment, with those recruited earlier receiving CPAP therapy and those recruited later receiving therapy with the C-Flex device. Follow-up assessments were conducted at 3 months. MEASUREMENTS AND RESULTS: The groups were similar demographically. The mean (+/- SD) treatment adherence over the 3-month follow-up period was higher in the C-Flex group compared to the CPAP group (weeks 2 to 4, 4.2 +/- 2.4 vs 3.5 +/- 2.8, respectively; weeks 9 to 12, 4.8 +/- 2.4 vs 3.1 +/- 2.8, respectively). Clinical outcomes and attitudes toward treatment (self-efficacy) were also measured. Change in subjective sleepiness and functional outcomes associated with sleep did not improve more in one group over the other. Self-efficacy showed a trend toward being higher at the follow-up in those patients who had been treated with the C-Flex device compared to CPAP treatment. CONCLUSIONS: Therapy with the C-Flex device may improve overall adherence over 3 months compared to standard therapy with CPAP. Clinical outcomes do not improve consistently, but C-Flex users may be more confident about their ability to adhere to treatment. Randomized clinical trials are needed to replicate these findings.     

Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes

BACKGROUND: Whereas a high prevalence of bronchial abnormalities has been reported in endurance athletes, its underlying mechanisms and consequences during exercise are still unclear. STUDY OBJECTIVES: The purpose of this study was to assess the following: (1) bronchial responsiveness to methacholine and to exercise; (2) airway inflammation; and (3) airflow limitation during intense exercise in endurance athletes with respiratory symptoms. DESIGN: Cross-sectional observational study. SETTING: Lung function and exercise laboratory at a university hospital. PATIENTS AND MEASUREMENTS: Thirty-nine endurance athletes and 13 sedentary control subjects were explored for the following: (1) self-reported respiratory symptoms; (2) bronchial hyperresponsiveness (BHR) to methacholine and exercise; (3) airflow limitation during intense exercise; and (4) bronchial inflammation using induced sputum and nitric oxide (NO) exhalation. RESULTS: Fifteen athletes (38%) showed BHR to methacholine and/or exercise in association with bronchial eosinophilia (mean [+/- SD] eosinophil count, 4.1 +/- 8.5% vs 0.3 +/- 0.9% vs 0%, respectively), higher NO concentrations (19 +/- 10 vs 14 +/- 4 vs 13 +/- 4 parts per billion, respectively), a higher prevalence of atopy, and more exercise-induced symptoms compared with non-hyperresponsive athletes and control subjects (p < 0.05). Furthermore, airflow limitation during intense exercise was observed in eight athletes, among whom five had BHR. Athletes with airflow limitation reported more symptoms and had FEV1, FEV1/FVC ratio, and forced expiratory flow at midexpiratory phase values of 14%, 9%, and 29%, respectively, lower compared with those of nonlimited athletes (p < 0.05). CONCLUSION: BHR in endurance athletes was associated with the criteria of eosinophilic airway inflammation and atopy, whereas airflow limitation during exercise was primarily a consequence of decreased resting spirometric values. Both BHR and bronchial obstruction at rest with subsequent expiratory flow limitation during exercise may promote respiratory symptoms during exercise in athletes.     

Targeting airway inflammation in asthma: current and future therapies

Asthma is a chronic inflammatory disease of the airway that requires long-term antiinflammatory therapy. Inhaled corticosteroids (ICSs) are recommended for first-line treatment of persistent disease, but not all patients achieve asthma control even when these agents are used in high doses and in combination with other medications, including a long-acting beta(2)-agonist or a leukotriene modifier. Such patients may require additional therapy. As information about asthma pathophysiology and inflammatory phenotypes continues to increase, and additional antiinflammatory options become available, it may be possible to target antiinflammatory therapy to various aspects of the disease and consequently to improve the treatment of patients with inadequate responses to standard ICS-based therapy. Several novel antiinflammatory therapies are in different stages of clinical development. The most clinically advanced of these is omalizumab, a recombinant humanized monoclonal antibody that specifically targets IgE and is indicated for patients with moderate-to-severe asthma caused by allergies. Omalizumab has demonstrated efficacy in patients with moderate-to-severe asthma and documented evidence of allergen sensitivity. Other key therapy options in clinical development either target proinflammatory cytokines (eg, interleukin-4 and tumor necrosis factor-alpha) or inflammatory cells (eg, T-helper type 2 cells and eosinophils). This review provides an overview of the current and future approaches targeting airway inflammation in patients with asthma.     

Prevalence and risks of chronic airway obstruction: a population cohort study in taiwan

BACKGROUND: This study investigated the prevalence, incidence, and hospitalization for chronic airway obstruction (CAO) in a population cohort. METHODS: Medical reimbursement claims from 1996 to 2002 based on a 1996 insured cohort of 167,372 persons from National Health Insurance, Taiwan, were used. We presented the chronological trends of CAO (International Classification of Diseases, Ninth Revision code 496) and the relationships between the CAO severity and age, sex, urbanization, and hospitalization and comorbidity for the population >/= 40 years old. RESULTS: The overall average annual prevalence and incidence rates were 2.48/100 and 0.66/100, respectively, for the population, among 4,568 patients with CAO cared during the study period. For the population aged >/= 70 years, the prevalence rates had a peak of 8.83/100 in 1998 and afterward remained a plateau until 2002. The corresponding incidence decreased from 2.48/100 to 1.62/100, and the hospitalization rate for them had a peak of 2.22/100 in 1999. The multivariate logistic regression analysis showed that the risk of hospitalization for CAO was higher for patients with the comorbidity of renal failure, coronary artery disease, and pneumonia and influenza, but lower with skin and joint disorders. CONCLUSIONS: The national insurance program promotes patient care and provides a proper pathway for surveillance and identification of CAO.     

Persistent airway obstruction after virus infection is not associated with airway inflammation

BACKGROUND: This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. METHODS: Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. RESULTS: Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1 percent predicted [Delta%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Delta%FEV1, > or = 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. CONCLUSION: Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.     

Silent upper airway resistance syndrome: prevalence in a mixed military population

STUDY OBJECTIVES: The upper airway resistance syndrome (UARS) is a recently described form of sleep-disordered breathing in which transient increases in upper airway resistance result in repetitive EEG arousals. UARS is not associated with apnea or diminished airflow, although snoring and excessive daytime somnolence (EDS) are common. This report describes a subset of patients with UARS diagnosed by polysomnography who do not manifest snoring, which we define as silent upper airway resistance syndrome (SUARS). DESIGN: A retrospective review of all polysomnographies performed at our sleep disorders center during 2000. SETTING: Sleep disorders center of a large, academic, military hospital. PATIENTS: Our center serves military personnel, military retirees, and their dependent families. INTERVENTIONS: Esophageal manometry during polysomnography was routinely performed on patients with hypersomnolence (Epworth sleepiness scale > 10) who demonstrated a total arousal index >or= 10/h and a respiratory disturbance index of < 5/h on prior polysomnography. UARS was definitely diagnosed in patients who demonstrated repetitive increased upper airway resistance (IUAR) associated with brief EEG arousals followed by normalization of esophageal pressure (Pes). IUAR was defined by a pattern of crescendo negative inspiratory Pes of 相似文献   

Roles of angiopoietin-1 and angiopoietin-2 on airway microvascular permeability in asthmatic patients

BACKGROUND: Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma. METHODS: Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 mug/d) or montelukast (10 mg) for 12 weeks. RESULTS: VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level. CONCLUSIONS: Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma.     

Prognosis of patients with heart failure and obstructive sleep apnea treated with continuous positive airway pressure

BACKGROUND: Therapy with continuous positive airway pressure (CPAP) provides several benefits for patients with heart failure (HF) complicated by obstructive sleep apnea (OSA). However, the effect on the prognosis of such patients remains unknown. Aims: To determine whether CPAP therapy and compliance affects the prognosis of HF patients with OSA. METHODS: We classified 88 patients with HF and moderate-to-severe OSA into a CPAP-treated group (n = 65) and an untreated group (n = 23), and then those treated with CPAP were further subclassified according to CPAP therapy compliance. The frequency of death and hospitalization was analyzed using multivariate analysis. RESULTS: During a mean (+/- SD) period of 25.3 +/- 15.3 months, 44.3% of the patients died or were hospitalized. Multivariate analysis showed that the risk for death and hospitalization was increased in the untreated group (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.07 to 3.68; p = 0.030) and in less compliant CPAP-treated patients (HR, 4.02; 95% CI, 1.33 to 12.2; p = 0.014). CONCLUSION: Therapy with CPAP significantly reduced the risk of death and hospitalization among patients with HF and OSA. However, reduced compliance with CPAP therapy was significantly associated with an increased risk of death and hospitalization.     

Differences in airway cytokine profile in severe asthma compared to moderate asthma

BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.     

End-tidal PCO2 abnormality and exercise limitation in patients with primary pulmonary hypertension

OBJECTIVES: Primary pulmonary hypertension (PPH) is a pulmonary vasculopathy resulting in exercise intolerance, usually due to dyspnea. We hypothesized that ventilation is increased during exercise in PPH relative to normal because the ventilated lung is underperfused, cardiac output increase is restricted, and arterial hypoxemia may develop. Our aim was to determine the size of the reduction in end-tidal Pco(2) (Petco(2)) as a reflection of the abnormality in ventilatory efficiency and ventilatory drive in PPH patients. METHODS: We performed cardiopulmonary exercise testing (CPET) in 52 PPH patients. All had hemodynamic measurements to confirm the diagnosis of PPH. A subgroup of 29 patients who underwent right-heart catheterization within 50 days of CPET were studied to compare their CPET responses to resting hemodynamics. Nine healthy volunteers matched for age and gender served as CPET control subjects. RESULTS: In PPH patients, the percentage of predicted peak oxygen uptake (Vo(2)) correlated significantly with mean pulmonary artery pressure (mPAP) [r = - 0.59, p = 0.0007, n = 29]. Petco(2) values at rest, anaerobic threshold (AT), and peak Vo(2) were proportionately reduced as percentage of predicted peak Vo(2) decreased (r = 0.66 to 0.72, p < 0.0001, n = 52). Petco(2) values at rest, AT, and peak Vo(2) were also reduced as mPAP increased (r = - 0.51 to - 0.53, p < 0.005, n = 29). In contrast to normal subjects in whom Petco(2) increased from rest to AT, Petco(2) decreased in PPH patients, except for two patients with mild PPH in whom there was no change. Also, Petco(2) increased rather than decreased further at the start of recovery, in contrast to normal. Although usually normal at rest, oxyhemoglobin saturation decreased during exercise in most PPH patients. CONCLUSIONS: In patients with PPH, Petco(2) at rest and exercise is significantly reduced in proportion to physiologic disease severity. The range of values is unusually low. Furthermore, the directional changes of Petco(2) during exercise and early recovery are in the opposite direction of normal.     

Continuous positive airway pressure therapy improves cardiovascular autonomic function for persons with sleep-disordered breathing

BACKGROUND: Sleep-disordered breathing (SDB) is an independent risk factor for cardiovascular morbidity. Dysfunction of the cardiovascular autonomic nervous system may be a potential mechanism whereby SDB is linked to cardiovascular disease. Repetitive sympathetic activation during apneic episodes may impair cardiovascular reflex function, and increased sympathetic activity can stimulate renin release. Given that patients with SDB may have reduced cardiovascular autonomic function, the purpose of this study was to determine whether treatment with continuous positive airway pressure (CPAP) for 6 weeks would improve autonomic function. METHODS: Twenty-nine participants with a diagnosis of SDB, who completed 6 weeks of CPAP therapy, were evaluated for cardiovascular autonomic nerve fiber function at baseline and post therapy. Autonomic function tests included the following: R-R interval variation during deep breathing measured by vector analysis (ie, mean circular resultant [MCR]) and expiration/inspiration (E/I) ratio; and the Valsalva maneuver. Participants were also evaluated prior to CPAP therapy for plasma renin activity levels. RESULTS: Participants in this study showed improved cardiovascular autonomic function after 6 weeks of treatment (baseline vs follow-up) as assessed by the mean (+/- SD) MCR (33.2 +/- 22.5 vs 36.9 +/- 24.2, respectively; p < 0.05) and E/I ratio (1.20 +/- 0.12 vs 1.24 +/- 0.14, respectively; p < 0.01). Improved vagal tone was also noted for subjects with elevated renin levels. CONCLUSIONS: Treatment of SDB with CPAP for 6 weeks improved vagal tone and may be beneficial in reducing the risk of developing clinical manifestations of cardiovascular autonomic dysfunction (eg, increased risk of mortality).     

Inspiratory muscle unloading by neurally adjusted ventilatory assist during maximal inspiratory efforts in healthy subjects

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation in which the ventilator is controlled by the electrical activity of the diaphragm (EAdi). During maximal inspirations, the pressure delivered can theoretically reach extreme levels that may cause harm to the lungs. The aims of this study were to evaluate whether NAVA could efficiently unload the respiratory muscles during maximal inspiratory efforts, and if a high level of NAVA would suppress EAdi without increasing lung-distending pressures. METHOD: In awake healthy subjects (n = 9), NAVA was applied at increasing levels in a stepwise fashion during quiet breathing and maximal inspirations. EAdi and airway pressure (Paw), esophageal pressure (Pes), and gastric pressure, flow, and volume were measured. RESULTS: During maximal inspirations with a high NAVA level, peak Paw was 37.1 +/- 11.0 cm H(2)O (mean +/- SD). This reduced Pes deflections from - 14.2 +/- 2.7 to 2.3 +/- 2.3 cm H(2)O (p < 0.001) and EAdi to 43 +/- 7% (p < 0.001), compared to maximal inspirations with no assist. At high NAVA levels, inspiratory capacity showed a modest increase of 11 +/- 11% (p = 0.024). CONCLUSION: In healthy subjects, NAVA can safely and efficiently unload the respiratory muscles during maximal inspiratory maneuvers, without failing to cycle-off ventilatory assist and without causing excessive lung distention. Despite maximal unloading of the diaphragm at high levels of NAVA, EAdi is still present and able to control the ventilator.     

The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function

BACKGROUND: Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS: A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS: The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS: The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.     

Normal bronchial blood flow in COPD is unaffected by inhaled corticosteroids and correlates with exhaled nitric oxide

BACKGROUND: In COPD patients, there is reduced vascularity and inflammation of the bronchi, which may have opposite effects on bronchial blood flow (QAW). We studied the relationship of QAW with the fraction of exhaled nitric oxide (FENO), which is a potent vasodilator. We also investigated the vascular response to budesonide and a beta(2)-agonist. METHODS: We measured QAW in 17 patients with COPD (mean [+/- SEM] age, 67 +/- 3 years; 10 male patients; mean FEV(1), 57 +/- 3% predicted; mean FEV(1)/FVC ratio, 54 +/- 4%), all of whom were ex-smokers, and in 16 age-matched nonsmoking volunteers (mean age, 64 +/- 4 years) and compared this to FENO. QAW was measured using the acetylene dilution method. RESULTS: Mean QAW was similar in patients with COPD (34.29 +/- 1.09 microL/mL/min) compared to healthy subjects (35.50 +/- 1.74 microL/mL/min; p > 0.05) and was not affected by long-term treatment (35.89 +/- 1.63 microL/mL/min) or short-term treatment (32.50 +/- 1.24 microL/mL/min; p < 0.05) with inhaled budesonide. QAW positively correlated with the diffusion of carbon monoxide (ie, carbon monoxide transfer coefficient: r = 0.74; p < 0.05). FENO levels were mildly elevated in steroid-treated patients (10.89 +/- 0.87 parts per billion [ppb]) and untreated patients (9.40 +/- 0.86 ppb) compared to the control group (8.22 +/- 0.57 ppb; p < 0.05) and were correlated with QAW (r = 0.6; p < 0.05). Ten minutes after the inhalation of 200 microg of albuterol, QAW was more elevated in healthy control subjects (59.33 +/- 2.40 microL/mL/min) compared to COPD patients (38.00 +/- 0.58 microL/mL/min; p < 0.05), indicating that COPD patients may have a reduced bronchial vascular reactivity. CONCLUSIONS: QAW is normal in COPD patients and is not affected by therapy with inhaled corticosteroids or beta(2)-agonists. In addition, QAW correlates with levels of FENO, which may have a regulatory role.