Differential timing of arousals in obstructive and central sleep apnea in patients with heart failure.

STUDY OBJECTIVES: In obstructive sleep apnea (OSA), arousals generally occur at apnea termination and help restore airflow. However, timing of arousals in central sleep apnea (CSA) has not been objectively quantified, and since arousals can persist even when CSA is alleviated, may not play the same defensive role as they do in OSA. We hypothesized that arousals following central events would occur longer after event termination than following obstructive events and would be related to circulation time. METHODS: We examined polysomnograms from 20 patients with heart failure (HF) (left ventricular ejection fraction ≤ 45%): 10 with OSA and 10 with CSA (apneahypopnea index ≥ 15). Twenty central or obstructive apneas or hypopneas were analyzed in each patient. RESULTS: Compared to the OSA group in whom arousals generally occurred at obstructive event termination, in the CSA group they occurred longer after central event termination (0.9 ± 1.1 versus 8.0 ± 4.1 s, p < 0.0001), but before peak hyperpnea. Time from arousal to peak hyperpnea did not differ between groups (4.3 ± 1.1 vs 4.8 ± 1.6 s, p = 0.416). Unlike the OSA group, latency from apnea termination to arousal correlated with circulation time in the CSA group (r = 0.793, p = 0.006). CONCLUSIONS: In HF patients with CSA, apnea-to-arousal latency is longer than in those with OSA, and arousals usually follow resumption of airflow. These observations provide evidence that arousals are less likely to act as a protective mechanism to facilitate resumption of airflow following apneas in CSA than in OSA.

Contrasting effects of lower body positive pressure on upper airways resistance and partial pressure of carbon dioxide in men with heart failure and obstructive or central sleep apnea.

OBJECTIVES: This study sought to test the effects of rostral fluid displacement from the legs on transpharyngeal resistance (Rph), minute volume of ventilation (Vmin), and partial pressure of carbon dioxide (PCO2) in men with heart failure (HF) and either obstructive (OSA) or central sleep apnea (CSA). BACKGROUND: Overnight rostral fluid shift relates to severity of OSA and CSA in men with HF. Rostral fluid displacement may facilitate OSA if it shifts into the neck and increases Rph, because pharyngeal obstruction causes OSA. Rostral fluid displacement may also facilitate CSA if it shifts into the lungs and induces reflex augmentation of ventilation and reduces PCO2, because a decrease in PCO2 below the apnea threshold causes CSA. METHODS: Men with HF were divided into those with mainly OSA (obstructive-dominant, n = 18) and those with mainly CSA (central-dominant, n = 10). While patients were supine, antishock trousers were deflated (control) or inflated for 15 min (lower body positive pressure [LBPP]) in random order. RESULTS: LBPP reduced leg fluid volume and increased neck circumference in both obstructive- and central-dominant groups. However, in contrast to the obstructive-dominant group in whom LBPP induced an increase in Rph, a decrease in Vmin, and an increase in PCO2, in the central-dominant group, LBPP induced a reduction in Rph, an increase in Vmin, and a reduction in PCO2. CONCLUSIONS: These findings suggest mechanisms by which rostral fluid shift contributes to the pathogenesis of OSA and CSA in men with HF. Rostral fluid shift could facilitate OSA if it induces pharyngeal obstruction, but could also facilitate CSA if it augments ventilation and lowers PCO2.

Dose-response curve to salbutamol during acute and chronic treatment with formoterol in COPD.

BACKGROUND: Use of short-acting ß(2)-agonists in chronic obstructive pulmonary disease (COPD) during treatment with long-acting ß(2)-agonists is recommended as needed, but its effectiveness is unclear. The purpose of this study was to assess the additional bronchodilating effect of increasing doses of salbutamol during acute and chronic treatment with formoterol in patients with COPD. METHODS: Ten patients with COPD underwent a dose-response curve to salbutamol (until 800 µg of cumulative dose) after a 1-week washout (baseline), 8 hours after the first administration of formoterol 12 µg (day 1), and after a 12-week and 24-week period of treatment with formoterol (12 µg twice daily by dry powder inhaler). Peak expiratory flow, forced expiratory volume in one second (FEV(1)), forced vital capacity, and inspiratory capacity were measured at the different periods of treatment and at different steps of the dose-response curve. RESULTS: Despite acute or chronic administration of formoterol, maximal values of peak expiratory flow, FEV(1), and forced vital capacity after 800 µg of salbutamol were unchanged compared with baseline. The baseline FEV(1) dose-response curve was steeper than that at day 1, week 12, or week 24 (P < 0.0001). Within each dose-response curve, FEV(1) was different only at baseline and at day 1 (P < 0.001), when FEV(1) was still greater at 800 µg than at 0 µg (P < 0.02). In contrast, the forced vital capacity dose-response curves were similar at the different periods, while within each dose-response curve, forced vital capacity was different in all instances (P < 0.001), always being higher at 800 µg than at 0 µg (P < 0.05). CONCLUSION: In patients with stable COPD, the maximal effect of salbutamol on peak expiratory flow, FEV(1), and forced vital capacity was unchanged after either acute or chronic treatment with formoterol. With increasing doses of salbutamol, FEV(1) increased only after acute administration of formoterol. Forced vital capacity also significantly improved during long-term treatment with formoterol.

Predictors of nocturnal oxyhemoglobin desaturation in COPD.

It would be useful to detect predictors of marked nocturnal oxyhemoglobin desaturation (NOD) among COPD patients, who do not have respiratory failure when awake and sleep apnea (SA). Stable COPD patients with awake Pa(O2) ≥ 60 mmHg and Pa(CO2) ≤ 45 mmHg underwent cardio-respiratory polysomnography to exclude SA and to assess NOD. The patients that spent more than 30% of night time with Sp(O2) < 90%, were defined desaturators (D), and the others non desaturators (ND). Pulmonary function testing was performed to determine lung volumes, maximal flow rates, lung diffusion capacity for carbon monoxide and maximal inspiratory and expiratory pressure (P(Imax) and P(Emax)). Negative expiratory pressure test was performed to assess tidal expiratory flow limitation. Supine pharyngometry was performed to determine upper airway size, shuttle walking test to assess exercise desaturation. Twenty-one patients were included in the study (18 male, age 66.0±7.2 years, Body Mass Index 25.9±4.4 kg/m(2), FEV(1) 47.2±16.4% pred., Pa(O2) 74.7±6.9 mmHg, Pa(CO2) 40.3±3.4 mmHg): 10 were D and 11 ND. Significant differences between the two groups were found in diurnal Pa(CO2) (D: 42.4±3.0 vs. ND: 38.3±2.6mmHg; p<0.01), diurnal Sp(O2) (D: 94.0±1.5 vs. ND: 95.9±0.9%; p<0.01), inspiratory capacity (IC) (D: 69.6±11.9 vs. ND: 87.0±17.7% pred.; p<0.05), and oro-pharyngeal junction area (OPJ) (D: 0.8±0.2 vs. ND: 1.2±0.3 cm(2); p<0.01). Among parameters related to marked NOD at the univariate analysis, [Formula: see text] and OPJ remained as independent predictors after stepwise multiple regression analysis. These findings indicate that previously unrecognized factors such as smaller upper airway caliber and lung dynamic hyperinflation are associated with marked NOD in stable COPD patients without daytime respiratory failure and SA.

Effects on small airway obstruction of long-term treatments with beclomethasone/formoterol hydrofluoroalkane (metered-dose inhaler) versus fluticasone/salmeterol (dry-powder inhaler) in asthma: a preliminary study.

New formulations of extrafine particles of long-acting beta-2 agonists plus inhaled corticosteroids (LABA + ICS) have been shown to reach peripheral regions of the lung. The aim of the study was to assess the effect on small airway obstruction of long-term treatments with two different LABA + ICS formulations in asthma. Ten subjects with moderate persistent asthma were enrolled. After a 4-week washout period they were treated in a randomized crossover design for 24 weeks with formoterol, 12 micrograms, and beclomethasone, 200 micrograms, hydrofluoroalkane (HFA; by metered-dose inhaler) b.i.d. (FB) or salmeterol, 50 micrograms, and fluticasone, 250 micrograms (by dry-powder inhaler), b.i.d. (SF). At baseline and at the end of each period subjects underwent an Asthma Control Test (ACT) and Pulmonary Function Testing. The N(2) phase III slope and closing volume (CV) during single-breath washout test and difference between the maximal expiratory flow rates with air and heliox at isovolume corresponding to 50% [Delta(heliox-air)MEF(50%)] were measured to assess changes on peripheral airways function. Two subjects dropped out and eight completed the study. After SF and FB, forced expiratory volume at 1 second (FEV(1); p < 0.01) and FEV(1)/forced vital capacity (FVC; p < 0.01 for SF and p < 0.05 for FB) increased when compared with baseline. Although both FB and SF treatments slightly increased delta(heliox-air)MEF(50% isovolume) versus baseline, only after FB the N(2) phase III slope and CV decreased from 1.61 ± 0.61%/L to 1.35 ± 0.49 N(2)%/L (p = 0.054) and from 0.98 ± 0.56 L to 0.88 ± 0.58 L (p < 0.05), respectively. ACT score raised from 19 ± 5 (baseline) to 23 ± 1 after FB (p < 0.02) and 23 ± 2 after SF (p < 0.05). When compared with baseline and in contrast to SF (50/250 micrograms b.i.d.), FB HFA (12/200 micrograms b.i.d.) significantly improved functional parameters reflecting small airway obstruction in asthmatic patients. Registered in the public trial registry at www.ClinicalTrials.gov identifier: NCT01255579.

Relationship between critical pressure and volume exhaled during negative pressure in awake subjects with sleep-disordered breathing.

BACKGROUND: Critical pressure (Pcrit) is considered a reliable parameter to evaluate the mechanical properties of the passive upper airway (UA) and is significantly increased in patients with obstructive sleep apnea-hypopnea (OSAH) compared with normal subjects. The volume exhaled in the first 0.5 s after application at the mouth of 5 cm H(2)O negative pressure at the onset of expiration (V,NEP(0.5)) during wakefulness has been used as a marker of UA collapsibility. The aim of this study was to investigate if there is a significant relationship between V,NEP(0.5) and Pcrit in normal subjects, snorers, and patients with OSAH. METHODS: Thirty men, 10 with OSAH (aged 64 +/- 9.1 years, BMI 32 +/- 4.9 kg/m(2), apnea-hypopnea index [AHI] 43.8 +/- 24, neck circumference 46.6 +/- 3.7 cm), 10 snorers (aged 68 +/- 11 years, BMI 26.6 +/- 4.6 kg/m(2), AHI 3.5 +/- 0.8, snoring time > or = 30% of sleep time, neck circumference 42.2 +/- 3.9 cm), and 10 controls (aged 67 +/- 12 years, BMI 25.4 +/- 2.2 kg/m(2), AHI 1.9 +/- 1.2, neck circumference 41.2 +/- 2.2 cm) underwent V,NEP(0.5) measurement in supine position while awake and Pcrit measurement during sleep. Correlation between V,NEP(0.5) and Pcrit was performed in all subjects. RESULTS: Controls had V,NEP(0.5) of 456 +/- 82 mL and Pcrit of -1.38 +/- 0.6 cm H(2)O, snorers had V,NEP(0.5) of 321 +/- 33 mL and Pcrit -0.55 +/- 0.3 cm H(2)O, and patients with OSAH showed V,NEP(0.5) of 295 +/- 67 mL and Pcrit of 0.99 +/- 1 cm H(2)O (P < .001 vs normal subjects). A strong correlation was found between V,NEP(0.5) and Pcrit (r(2) = 0.61, P < .0001). CONCLUSIONS: In males with neck circumference > 37 cm, V,NEP(0.5) during wakefulness strongly reflects Pcrit in a wide range of values. Our findings suggest that V,NEP(0.5) can be used as valuable substitute for Pcrit to assess UA collapsibility for clinical and research purposes in these subjects.

Short- and long-term effects of CPAP on upper airway anatomy and collapsibility in OSAH.

RATIONALE AND AIM: In obstructive sleep apnea hypopnea (OSAH) patients, an increase of upper airway (UA) collapsibility has been described together with a reduced UA caliber due to inflammation, edema, and fat accumulation in pharyngeal walls. CPAP is the main treatment of OSAH and acts mechanically by increasing pressure inside UA. The aim of this study was to assess the short- and long-term effects of CPAP on UA caliber and collapsibility in severe OSAH patients. PATIENTS AND METHODS: Ten obese patients (nine male, age 55+/- 9 yr, BMI 35.1 +/- 6.1, Epworth sleepiness scale 12.3 +/- 3.6 point, AHI 58.8 +/- 27.1) had measurements of oropharingeal junction area (OPJ), mean pharyngeal area (APmean), maximal pharyngeal area (APmax) by acoustic pharyngometry and determination of expired volume in the first 0.5 s after the application at the mouth of -5 cmH(2)O negative expiratory pressure (V,NEP(0.5)) during wakefulness in the supine position under basal conditions (baseline) and after 1 week and 6 months of CPAP treatment. RESULTS: OPJ was 0.74 +/- 0.28 cm(2) at baseline, 0.90 +/- 0.24 cm(2) after 1 week and 1.05 +/- 0.31 cm(2) after 6 months (1 week and 6 months vs baseline p < 0.05). APmax was 2.28 +/- 0.74 cm(2) at baseline, 2.79 +/- 0.90 cm(2) after 1 week and 2.94 +/- 0.33 cm(2) after 6 months (1 week and 6 months vs baseline p < 0.05). APmean was 1.43 +/- 0.46 cm(2) at baseline, 1.82 +/- 0.45 cm(2) after 1 week and 1.94 +/- 0.35 cm(2) after 6 months (1 week vs baseline p < 0.01; 6 months vs baseline; p < 0.05). V,NEP(0.5) was 290 +/- 73 mL at baseline, 291 +/- 65 mL after 1 week and 338 +/- 67 mL after 6 months (6 months vs baseline p < 0.05; 1 week vs 6 months p < 0.01). CONCLUSIONS: Our data suggest that CPAP treatment might be effective in OSAH patients not only by causing a mechanical splint of UA but also by inducing an improvement on anatomical (early) and functional (later on) aspects of UA that can be observed during wakefulness.