Corticosteroids do not affect the clinical or physiological status of infants with bronchiolitis

The treatment of infants aged 1.5-11.0 months suffering from acute bronchiolitis with a combination of inhaled albuterol and systemic corticosteroids or inhaled albuterol and placebo was compared in 50 infants in a double blind study. The mean initial clinical score and the rate of improvement was similar in the two groups. The mean +/- SD hospital stay was 5.0 +/- 1.2 days for the steroid group and 5.2 +/- 1.7 days for the placebo group. Lung function was measured in 14 infants (7 from each group) and showed evidence of increased lung volumes and severe airway obstruction in the acute stage (the mean values for the steroid group were: TGV, 31 mL/kg; SGaw, 0.104 L/s.cmH2O; VmaxFRC, 12.9 mL/s/kg; for the placebo group: TGV, 35 mL/kg; SGaw, 0.104 L/s.cmH2O; VmaxFRC, 8.5 mL/s/kg) which had improved 2-4 weeks later (steroid group: TGV, 25 mL/kg; SGaw, 0.168 L/s.cmH2O; VmaxFRC, 21.6 mL/s/kg; -placebo group: TGV, 24 mL/kg, SGaw, 0.198 L/s.cmH2O, VmaxFRC, 17.5 mL/s/kg). There were no significant differences of thoracic gas volume, specific airway conductance, and forced expiratory flow at resting lung volume between the two groups, either in the acute or convalescent stages. We conclude that corticosteroids do not change the rate of clinical improvement in acute bronchiolitis, nor do they effect lung function 2-4 weeks later.     

Regulation of airway smooth muscle tone in sleeping dogs.

We examined the influence of sleep state on airway smooth muscle tone in 4 unanesthetized dogs that were trained to sleep in the laboratory. The dogs had been prepared with a permanent side-hole tracheostomy and bilateral cervical vagal loops. During the studies, the dogs breathed through a cuffed endotracheal tube inserted through the tracheostomy. To monitor changes in tracheal smooth muscle tone, we measured the pressure in the water-filled cuff of the endotracheal tube. The technique was validated by examining changes in cuff pressure after administration to the dogs of a series of chemical agents and physiologic stimuli known to constrict or relax tracheobronchial smooth muscle. Sleep state of the dogs was determined by behavioral, electroencephalographic, and electromyographic criteria. During quiet wakefulness, tracheal smooth muscle tone was stable. With the onset and progression of sleep through the nonrapid-eye movement stages, airway smooth muscle tone relaxed (decrease in cuff pressure of 20 to 40 cm H2O), reaching a new steady level during slow-wave sleep. In contrast, during rapid-eye-movement sleep, tracheal smooth muscle tone fluctuated markedly and erratically, as reflected by changes in cuff pressure as large as 90 cm H2O. Partial blockade of the vagus nerves, by cooling the exteriorized cervical vagal loops, decreased or abolished the fluctuations in tracheal smooth muscle tone during rapid-eye-movement sleep at temperatures that did not abolish resting tone, demonstrating that the changes in tone during rapid-eye-movement sleep were related to variability in neural control of airway smooth muscle.     

Effect of nasal or oral breathing route on upper airway resistance during sleep.

Healthy subjects with normal nasal resistance breathe almost exclusively through the nose during sleep. This study tested the hypothesis that a mechanical advantage might explain this preponderance of nasal over oral breathing during sleep. A randomised, single-blind, crossover design was used to compare upper airway resistance during sleep in the nasal and oral breathing conditions in 12 (seven male) healthy subjects with normal nasal resistance, aged 30+/-4 (mean+/-SEM) yrs, and with a body mass index of 23+/-1 kg x m2. During wakefulness, upper airway resistance was similar between the oral and nasal breathing routes. However, during sleep (supine, stage two) upper airway resistance was much higher while breathing orally (median 12.4 cmH2O x L(-1) x s(-1), range 4.5-40.2) than nasally (5.2 cmH2O x L(-1) x s(-1), 1.7-10.8). In addition, obstructive (but not central) apnoeas and hypopnoeas were profoundly more frequent when breathing orally (apnoea-hypopnoea index 43+/-6) than nasally (1.5+/-0.5). Upper airway resistance during sleep and the propensity to obstructive sleep apnoea are significantly lower while breathing nasally rather than orally. This mechanical advantage may explain the preponderance of nasal breathing during sleep in normal subjects.     

Relationship between upper airway and inspiratory pump muscle force in obstructive sleep apnea

BACKGROUND: Upper airway (UA) patency during inspiration is determined by the balance between dilating forces generated by UA dilator muscle activity and collapsing forces related to the decreased intraluminal pressure that accompanies flow generated by inspiratory muscle activity. It is possible that the relative strengths of UA dilator and inspiratory pump muscles could be an important determinant of the susceptibility to UA collapse during sleep (ie, obstructive sleep apnea [OSA]). METHODS: Measurements of tongue protrusion (TP) force and maximum inspiratory pressure (Pimax) were obtained in 94 patients admitted for overnight polysomnography for suspected OSA, quantified by apnea-hypopnea index (AHI). RESULTS: There was a direct linear relationship between TP force and Pimax (r(2) = 0.37, p < 0.001). A high ratio of TP force to Pimax (greater than group 90th percentile, 0.027 kg/cm H(2)O) appeared to protect against OSA, as moderate-to-severe OSA (AHI > 20/h) was not observed in any individual with a ratio above this threshold. AHI was not linearly related to TP force, Pimax, or the ratio of TP force to Pimax. CONCLUSIONS: UA muscle strength is linearly related to inspiratory pump muscle strength. The ratio of UA muscle strength (TP force) and inspiratory pump muscle strength (Pimax) was not different between individuals with and without OSA; however, a high wakeful ratio of TP force to Pimax appears to be associated with a reduced propensity to moderate-to-severe OSA.     

Endothelium-dependent relaxing factors do not affect the smooth muscle of portal-mesenteric veins

Experiments were designed to analyze the difference in endothelium-dependent responsiveness to acetylcholine between arteries and veins. The effect of endothelium-derived relaxing factor(s) released from femoral arteries of the dog was compared on the coronary artery of the dog, the aorta of the rat, and portal-mesenteric veins of both species. Endothelium-derived relaxing factor(s) released by canine femoral arteries induced comparable relaxation of the canine coronary artery and the aorta of the rat. However, neither the canine nor the rat portal vein relaxed when exposed to endothelium-derived relaxing factor(s) released by the femoral arterial segments. Endothelium-derived relaxing factor(s) did not affect the action potentials and the spontaneous activity of the rat portal vein. Sodium nitroprusside induced complete relaxation of the canine coronary artery but failed to abolish the spontaneously evoked contractions of the portal veins. These experiments suggest that the longitudinal smooth muscle of portal veins is insensitive to endothelium-derived relaxing factor(s), presumably because of a different sensitivity of guanylate cyclase. Endothelium-derived relaxing factor does not possess calcium-entry blocking properties.     

Nasal CPAP therapy, upper airway muscle activation, and obstructive sleep apnea

In treating obstructive sleep apnea, positive pressure applied through the nose (CPAP) might cause a reflex increase in upper airway muscle activity or might enlarge the airway passively. We studied the effect of CPAP applied by a nasal mask on the electromyographic (EMG) activation of the alae nasi and genioglossal muscles in 8 patients with obstructive apneas during sleep, and correlated EMG activity with concentrations of oxygenation by ear oximeter, and with the end-expiratory position of the rib cage and abdomen by DC-coupled inductance plethysmography. One to 3 cm H2O of CPAP did not eliminate the cyclic occurrence of obstructive apneas. The greatest tonic and phasic EMG activity occurred at apnea termination; the least occurred at apnea onset. With 13 to 15 cm H2O CPAP, apneas were eliminated; mean oxygen saturation rose from 84 +/- 6% (mean +/- SD) to 92 +/- 2%, and EMG activity was reduced or eliminated. With abrupt lowering of CPAP, end-expiratory positions fell, and an obstructive apnea ensued; however, EMG activity did not immediately return. We conclude that the elimination of apneas with CPAP is not attributed to increased EMG activity in the upper airway. The reduction in EMG activity observed with nasal CPAP was closely related to the improvement in hemoglobin oxygen saturation. Therefore, CPAP may act as a pneumatic splint and passively open the upper airway to prevent obstructive apnea.     

Inhibition of airway smooth muscle tone by Chinese herbal medicines.

The aim of the present study was to elucidate whether Chinese traditional herbal drugs, Gorei-San (TJ-17) and Toki-Shakuyaku-San (TJ-23), affect airway smooth muscle tone and, if so, to determine what the mechanism of action is. Rabbit tracheal segments were isolated and the contractile responses to electrical field stimulation and acetylcholine were measured before and after the application of TJ-17 or TJ-23 under isometric conditions in vitro. Ouabain-sensitive rubidium-86 (86Rb) uptake by tissues in response to each drug was also measured. Each herbal medicine attenuated the contractile responses to electrical field stimulation and acetylcholine in a concentration-dependent manner, the maximal inhibition of acetylcholine-induced contraction being 37.5+/-4.9% for TJ-17 and 42.4+/-5.3% for TJ-23 (p<0.05 for each). These effects were not altered by mechanical removal of the epithelium, indomethacin, the nitric oxide synthase inhibitor NG -nitro-L-arginine methyl ester, the cyclic adenosine monophosphate (cAMP)-dependent protein kinase inhibitor adenosine 3'5'-cyclic monophosphorothioate (Rp-cAMPS), the cyclic guanosine monophosphate (cGMP)-dependent protein kinase inhibitor KT5823, or the calcium (Ca2+)-activated potassium (K+) channel inhibitor charybdotoxin, but were greatly inhibited in the presence of the sodium (Na+)-K+ adenosine triphosphatase (ATPase) inhibitor ouabain. Incubation of tissues with TJ-17 and TJ-23 dose dependently increased ouabain-sensitive 86Rb uptake. The results of the study suggest that both Gorei-San and Toki-Shakuyaku-San reduce airway smooth muscle tone via a postjunctional mechanism probably through stimulation of the sodium pump and the subsequent hyperpolarization/repolarization of the cell membrane. These effects may contribute to the antiasthmatic properties of these herbal medicines.     

Ozone-induced lung function decrements do not correlate with early airway inflammatory or antioxidant responses.

This study sought to clarify the early events occurring within the airways of healthy human subjects performing moderate intermittent exercise following ozone challenge. Thirteen healthy nonsmoking subjects were exposed in a single blinded, crossover control fashion to 0.2 parts per million (ppm) O3 and filtered air for 2 h, using a standard intermittent exercise and rest protocol. Lung function was assessed pre- and immediately post-exposure. Bronchoscopy was performed with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) 1.5 h after the end of the exposure period. Respiratory tract lining fluid (RTLF) redox status was assessed by measuring a range of antioxidants and oxidative damage markers in BW and BAL fluid samples. There was a significant upregulation after O3 exposure in the expression of vascular endothelial P-selectin (p<0.005) and intercellular adhesion molecule-1 (p<0.005). This was associated with a 2-fold increase in submucosal mast cells (p<0.005) in biopsy samples, without evidence of neutrophilic inflammation, and a decrease in BAL fluid macrophage numbers (1.6-fold, p<0.005), with an activation of the remaining macrophage subset (2.5-fold increase in % human leukocyte antigen (HLA)-DR+ cells, p<0.005). In addition, exposure led to a 4.5-fold and 3.1-fold increase of reduced glutathione (GSH) concentrations, in BW and BAL fluid respectively (p<0.05), with alterations in urate and alpha-tocopherol plasma/RTLF partitioning ratios (p<0.05). Spirometry showed reductions in forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.01), with evidence of small airway narrowing using forced expiratory flow values (p<0.005). Evidence was found of O3-induced early adhesion molecule upregulation, increased submucosal mast cell numbers and alterations to the respiratory tract lining fluid redox status. No clear relationship was demonstrable between changes in these early markers and the lung function decrements observed. The results therefore indicate that the initial lung function decrements are not predictive of, or causally related to the O3-induced inflammatory events in normal human subjects.     

Androgen blockade does not affect sleep-disordered breathing or chemosensitivity in men with obstructive sleep apnea.

As sleep apnea is more prevalent in men and testosterone has known effects on sleep apnea and chemosensitivity, reduction of androgen activity may influence sleep-disordered breathing and respiratory control. We studied the effect of 1 wk of treatment with flutamide, a nonsteroidal antiandrogen, on sleep, respiration, and ventilatory control in eight men with sleep apnea. Results on flutamide were compared with two baseline studies performed before and after the drug treatment period. Although effective androgen blockade was achieved as evidenced by increased hormone levels, flutamide had no effect on sleep architecture or chemoresponsiveness to hypoxia and hypercapnia. There was a trend towards a reduction in respiratory disturbance index in both NREM and REM sleep (41 +/- 4 baseline versus 34 +/- 3 flutamide, p = 0.09 NREM; 53 +/- 4 baseline versus 48 +/- 3 flutamide, p = 0.16 REM), but this was not significant. Our results indicate that androgen blockade had no clinically significant effect on sleep, sleep-disordered breathing, or chemosensitivity in patients with moderate to severe sleep apnea. More specific blockers such as gonadotrophin-releasing hormone analogs may have more clinical effect or, alternatively, androgen blockade may be more beneficial in patients with milder sleep apnea.     

Effects of upper airway carbon dioxide on upper airway resistance and muscle activity in young guinea-pigs.

The upper airway (UA) of adult animals is known to contain carbon dioxide-sensitive receptors and UA CO2 reflexly affects breathing, UA dilator muscle activity and UA resistance. These effects may function in the control of UA patency. There is evidence that some UA reflexes are stronger in young than in adult animals, but it is not known whether CO2-sensitive receptors are present in the UA of young animals, and the effects of UA CO2 on UA resistance and on UA dilator muscle activity have not been investigated in young animals. The responses of ventilation, UA resistance and geniohyoid muscle electromyographic activity to warm air containing 10% CO2 applied to the isolated UA were measured in anaesthetized, vagotomized young guinea-pigs breathing spontaneously through a low-cervical tracheostomy. Upper airway carbon dioxide caused an increase in ventilation (46.7+/-16.3 to 49.9+/-16.8 mL x min(-1) x 100 g body weight(-1)) and upper airway resistance (56.8+/-14.8 to 63.7+/-17.7 cmH2O x L(-1) x s(-1) x kg body weight(-1)). Similar effects were obtained following vagotomy. Geniohyoid activity became apparent following vagotomy and this activity was reduced by upper airway carbon dioxide. These responses were abolished by topical anaesthesia of the upper airway. This suggests that the reflexes seen are due to carbon dioxide-sensitive receptors in the upper airway.     

Methods for increasing upper airway muscle tonus in treating obstructive sleep apnea: systematic review

Objective  

Treatment of obstructive sleep apnea (OSA) using methods for increasing upper airway muscle tonus has been controversial and poorly reported. Thus, a review of the evidence is needed to evaluate the effectiveness of these methods.     

Evaluation of a simplified oscillation technique for assessing airway obstruction in sleep apnoea.

The forced oscillation technique (FOT) is a noninvasive method that is useful for assessing airway obstruction and for titrating continuous positive airway pressure (CPAP) in patients with sleep apnoea. The aim was to evaluate the routine applicability of a simplified FOT set-up based on recording pressure and flow at the level of the CPAP device, i.e. obviating the need for connecting the transducers to the nasal mask. A correction to account for the tubing and the exhaust port was applied. This simplified FOT was evaluated on nine patients with moderate or severe sleep apnoea during routine CPAP titration. Patient impedance measured by the simplified FOT ([Z]) was compared with actual patient impedance ([Zrs]) measured simultaneously with a reference FOT based on recording pressure and flow at the nasal mask. An excellent agreement was found between [Z] and [Zrs] over the wide range of airway obstruction explored (4.8-72.1 cmH2O x s x L(-1)): [Z] = [Zrs] x 0.86 + 1.3 cmH2O x s x L(-1) (r = 0.99). Moreover, the simplified and the conventional FOT settings detected the same respiratory events during sleep. These results demonstrate that this simplified FOT is applicable for measuring airway obstruction during routine sleep studies in patients with sleep apnoea.     

Lethal concentrations of mercury or lead do not affect coagulation kinetics in human plasma

Journal of Thrombosis and Thrombolysis -     

Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep.

The aim of the present study was to evaluate the degree and duration of respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in sleep-disordered breathing. Ten postmenopausal females with predominantly partial upper airway obstruction during sleep had an overnight sleep study at baseline, on the fourteenth day of treatment with MPA and after a 3-week washout period. Six subjects on nCPAP were also studied 3 months later. At baseline, the overnight mean+/-SD end-tidal pressure of carbon dioxide (Pet,CO2) was 5.5+/-0.4 kPa the arterial oxygen saturation (Sa,O2) 93.0+/-1.2%, Sa,O2 nadir 80.0+/-6.7%, and frequency of oxygen desaturation > or = 4% (ODI4) per hour 2.2+/-1.3. MPA decreased Pet,CO2 by 0.8 kPa (14.5%, p<0.001). After washout, the mean Pet,CO2 remained at 0.5 kPa (9.1%, p<0.001) lower than at baseline. Sa,O2 did not change. Pet,CO2 was lower on MPA than on nCPAP (4.7+/-0.2 kPa versus 5.0+/-0.3 kPa; p=0.037) but Sa,O2 was similar. Apnoea/hypopnoea index tended to be lower on CPAP than on MPA. Medroxyprogesterone acetate at a daily dose of 60 mg improves ventilation in postmenopausal females with partial upper airway obstruction during sleep without compromising sleep. The ventilatory improvement is sustained for at least 3 weeks posttreatment. Medroxyprogesterone acetate was more efficient in decreasing the partial pressure of carbon dioxide but continuous positive airway pressure was superior in decreasing respiratory efforts.     

Effect of uvulopalatopharyngoplasty on upper airway collapsibility in obstructive sleep apnea.

Previous investigators have demonstrated variable responses to uvulopalatopharyngoplasty (UPP) in patients with obstructive sleep apnea. We hypothesized that this variability is due to either (1) differences in baseline pharyngeal collapsibility preoperatively or (2) differences in magnitude of the decrease in pharyngeal collapsibility resulting from surgery. To determine the relationship between changes in collapsibility and the response to UPP surgery, we measured the upper airway critical pressure (Pcrit) before and after UPP in 13 patients with obstructive sleep apnea. During non-REM sleep, maximal inspiratory airflow (VImax) was quantitated by varying the level of nasal pressure (PN), and Pcrit was determined by the level of PN below which VImax ceased. A positive response to UPP was defined by a greater than or equal to 50% fall in non-REM disordered breathing rate (DBR). In the entire group, UPP resulted in significant decreases in DBR from 71.1 +/- 22.4 to 44.7 +/- 38.4 episodes/h (p = 0.025) and in Pcrit from 0.2 +/- 2.4 to -3.1 +/- 5.4 cm H2O (p = 0.016). Moreover, the percent change in DBR was correlated significantly with the change in Pcrit (p = 0.001). Subgroup analysis of responders and nonresponders demonstrated that significant differences in Pcrit were confined to the responders. Specifically, responders demonstrated a significant fall in Pcrit from -0.8 +/- 3.0 to -7.3 +/- 4.9 cm H2O (p = 0.01), whereas no significant change in Pcrit was detected in the nonresponders (1.1 +/- 1.6 versus 0.6 +/- 2.0 cm H2O. No clinical, polysomnographic, or physiologic predictors of a favorable response were found preoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reliability of measurements of muscle tone and muscle power in stroke patients

OBJECTIVES: to establish the reliability of the modified Ashworth scale for measuring muscle tone in a range of muscle groups (elbow, wrist, knee and ankle; flexors and extensors) and of the Medical Research Council scale for measuring muscle power in the same muscle groups and their direct antagonists. DESIGN: a cross-sectional study involving repeated measures by two raters. We estimated reliability using the kappa statistic with quadratic weights (Kw). SETTING: an acute stroke ward, a stroke rehabilitation unit and a continuing care facility. SUBJECTS: people admitted to hospital with an acute stroke-35 patients, median age 73 (interquartile range 65-80), 20 men and 15 women. RESULTS: inter- and intra-rater agreement for the measurement of power was good to very good for all tested muscle groups (Kw = 0.84-0.96, Kw = 0.70-0.96). Inter- and intra-rater agreement for the measurement of tone in the elbow, wrist and knee flexors was good to very good (Kw = 0.73-0.96, Kw = 0.77-0.94). Inter- and intra-rater agreement for the measurement of tone in the ankle plantarflexors was moderate to good (Kw = 0.45-0.51, Kw = 0.59-0.64). CONCLUSIONS: the Medical Research Council scale was reliable in the tested muscle groups. The modified Ashworth scale demonstrated reliability in all tested muscle groups except the ankle plantarflexors. If reliable measurement of tone at the ankle is required for a specific purpose (e.g. to measure the effect of therapeutic intervention), further work will be necessary.