Effectiveness of glycopyrronium bromide in the treatment of small airway dysfunction: A retrospective study.

Objective: Glycopyrronium bromide has a quaternary ammonium structure and a low oral bioavailability, which reduces its systemic effects; it acts through a bronchodilating blockade of muscarinic receptors. The aim of this retrospective study was to analyze a possible relationship between the changes in the small airways and the efficacy of a bronchodilation with glycopyrronium bromide; exercise tolerance was also assessed, by performing the six-minute walking test. Methods: Forty-one patients were identified (23 females/18 males; mean age 66.82 ± 9.75 years), with a normal forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of 77.45% ± 4.86%, a reduced forced mid-expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of 42.9% ± 10.5%, with an increased residual volume/total lung capacity ratio of 132.68% ± 6.41%, FEV1 1.85 ± 0.54 L, forced vital capacity 2.39 ± 0.71 L, airway resistance (sR tot) 168.18% ± 42.5%, total lung capacity 98.28% ± 8.9%, six-minute walking test distance 318.3 ± 36.6 m, modified British Medical Research Council dyspnea scale 1.48 ± 0.77. All patients were initiated with glycopyrronium bromide 50 µg/die and reassessed after 4 months. Results: After the treatment with glycopyrronium bromide, a significant improvement was noted regarding forced vital capacity (p = 0.04), FEF25-75 (p < 0.001), sR tot (p < 0.001), residual volume/total lung capacity ratio (p < 0.001) with reduction of dynamic hyperinflation, the significant increase of the distance covered during the six-minute walking test (p < 0.001), and modified British Medical Research Council (p < 0.001) showed enhanced exercise tolerance. FEV1 improved, but the difference was not statistically significant. Conclusions: Small airway dysfunction is associated with bronchodilator responsiveness. Glycopyrronium bromide has proven to be capable of inducing favorable effects on lung hyperinflation and its functional and clinical consequences, with a decrease in dyspnea and an increase in exercise capacity. The use of anticholinergic drugs is useful in the management of small airway disease.

The Respiratory "Overlap Syndrome": Efficacy and Usefulness of the Combined Double Bronchodilation.

The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome in a single patient is known as "overlap syndrome," and worsens the prognosis of the affected subjects. A marked bronchodilation may be useful for the treatment of this condition. In fact, as stated in the GOLD 2017 guidelines, the combination of indacaterol/glycopyrronium may exert positive synergistic effects on smooth muscle cell and airway resistance, with a more pronounced efficiency in reducing lung hyperinflation. Noteworthy, inhaled bronchodilators favorably alter the dynamically determined components of resting lung hyperinflation and help deflate the overinflated lungs. This is particularly important in order to improve dyspnea, exercise performance, and night saturation, especially when combined with continuous positive airway pressure ventilation, as reported in our case series. We report 3 cases of patients with COPD in a stable clinical condition, referred to the Department of Respiratory Pathophysiology at the "Mariano Santo" Hospital in Cosenza, due to possible symptoms suggestive of obstructive sleep apnea, and who were successfully treated with indacaterol/glycopyrronium at a fixed dose.

Abnormal thyroid hormones and non-thyroidal illness syndrome in obstructive sleep apnea, and effects of CPAP treatment.

OBJECTIVE: In obstructive sleep apnea (OSA), while both hypothyroidism and hyperthyroidism have been studied, the occurrence of non-thyroidal illness syndrome (NTIS) (normal thyroid stimulating hormone [TSH] with low triiodotironine) has not been investigated. We explored the occurrence of NTIS in patients with moderate to severe OSA and its relationship to the severity of nocturnal respiratory disorders. We also studied the occurrence of subclinical hypothyroidism (SH, ie, high TSH with normal thyroxine) in OSA and changes in circulating TSH, free triiodotironine (fT3) and free thyroxine (fT4) after CPAP treatment. METHODS: After a nocturnal respiratory polysomnography, 125 consecutive patients with moderate to severe OSA and 60 control subjects with normal nocturnal respiration were recruited. Morning circulating TSH, fT3, and fT4 were measured in all subjects. In a subsample of patients, nocturnal polysomnography and hormonal determinations were repeated after CPAP treatment for five months. RESULTS: NTIS was found in 13 (10.4%), and SH in ten (8%) OSA subjects, but not in any control subjects. Patients with NTIS showed worse mean nocturnal oxygen saturation and time with saturation <90% (both p < 0.001). After treatment, NTIS subjects (n = 13) showed an increase in fT3 (p < 0.001) to the normal range, and SH subjects (n = 6) a slight decrease in TSH (p = 0.01). In the patients with normal hormones before treatment (n = 45), no change was observed. CONCLUSIONS: NTIS may occur in OSA patients with severe nocturnal hypoxemia. OSA treatment is followed by an improvement in TSH in patients with abnormal baseline levels of this hormone, and by recovery of NTIS.

Analysis of NREM sleep in children with Prader-Willi syndrome and the effect of growth hormone treatment.

OBJECTIVES: Only few studies are available in the literature on sleep in children with Prader-Willi syndrome (PWS) and one single study analyzed the cyclic alternating pattern (CAP) in young adults with PWS, showing that patients with a higher proportion of A1 subtypes presented less severe GH deficiency. The aims of our study were to evaluate CAP in children with PWS compared to an age-matched control group and to evaluate the differences between PWS children with (GH+) and without (GH-) GH therapy. METHODS: Laboratory polysomnographic sleep recordings were obtained from 30 children with PWS (17 GH- and 13 GH+ patients) and 15 age-matched normal controls. RESULTS: Compared to controls, PWS children had a reduction of sleep efficiency, of sleep stage 2 and of REM sleep. GH- PWS patients showed a global decrease in total CAP rate during S1 and S2 but not in SWS. In GH+ PWS patients, SWS CAP rate and A1 index were increased vs. GH- children. DISCUSSION: The decrease in total CAP rate and all A subtypes might suggest the presence of a decreased NREM sleep instability in our PWS children and can be considered to be in agreement with the reported generalized hypoarousal state of PWS subjects. GH therapy is likely to increase CAP rate and A1 index during SWS in PWS patients.

Noninvasive ventilation in children with spinal muscular atrophy types 1 and 2.

OBJECTIVE: Our aim was to assess the efficacy of noninvasive ventilation (NIV) for the treatment of thoracoabdominal asynchrony during sleep in children with spinal muscular atrophy (SMA) types 1 and 2. DESIGN: Nine subjects underwent assessment for sleep apnea/hypopnea index (AHI), mean oxyhemoglobin saturation (SpO2), oxygen desaturation index, transcutaneous carbon dioxide tension (tcpCO2), and mean phase angle during sleep as a measure of thoracoabdominal coordination. A second sleep study was performed with use of NIV. RESULTS: The nine patients (7 mos of age, range 2-33) had a baseline AHI of 2.1 events per hour (range 0.5-55.8), oxygen desaturation index of 3.7 events per hour (range 1.6-46.1), mean tcpCO2 of 46 mm Hg (range 37-60), and phase angle of 127 degrees (range 72.7-151.7). Comparing baseline and NIV sleep studies, we found significant improvement in oxygen desaturation index (P < 0.010), mean tcpCO2 (P < 0.001), and phase angle (P < 0.001). For five patients, phase-angle improvement became significant when using high-span bilevel positive airway pressure (PAP). CONCLUSIONS: NIV improved sleep breathing parameters and thoracoabdominal coordination during sleep in SMA types 1 and 2. Phase-angle improvement correlated with bilevel PAP pressures. Phase angle may be useful for the evaluation and monitoring of therapeutic interventions such as NIV.

Sleep-disordered breathing in spinal muscular atrophy types 1 and 2.

OBJECTIVE: Our aim was to assess the respiratory pattern during sleep in patients affected by spinal muscular atrophy types 1 and 2 and to compare their apnea-hypopnea indices with those of controls. DESIGN: All consecutively referred patients underwent polysomnography. Sleep stages were defined as either wake, quiet sleep (QS), or active sleep (AS). As measures of thoracoabdominal coordination, we measured: phase angle during QS and AS (Ph Angle QS and AS), phase relation during inspiration and expiration during QS and AS: (Ph RIB QS, Ph RIB AS, Ph REB QS; Ph REB AS) and the apnea-hypopnea index. RESULTS: The 14 consecutively referred infants and small children (age, 11.7 +/- 11.4 mos) showed a higher apnea-hypopnea index (P < 0.001), Ph Angle QS (P < 0.001), Ph Angle AS (P < 0.001), Ph RIB QS (P < 0.001), Ph RIB AS (P < 0.001), Ph REB QS (P < 0.001), and Ph REB AS (P < 0.001) compared with 28 healthy controls (age, 10.1 +/- 8.9 mos). CONCLUSIONS: Patients affected by types 1 and 2 spinal muscular atrophy had significantly higher apnea-hypopnea indices than controls. Thoracoabdominal asynchrony was present during the inspiratory and expiratory phases in both quiet and active sleep. Measures of thoracoabdominal coordination may be useful for the evaluation and monitoring of therapeutic interventions for these patients.

Does cognitive dysfunction conform to a distinctive pattern in obstructive sleep apnea syndrome?

Obstructive sleep apnea (OSA) is a recognized cause of cognitive dysfunction. By using a cross-sectional comparative study, we aimed to verify whether neuropsychological performance of untreated OSA patients conforms to a distinctive pattern. Forty-nine newly diagnosed, untreated OSA patients, 27 with multi-infarctual dementia (MID), 31 with mild to moderate dementia of Alzheimer type (DAT) and 63 with severe chronic obstructive pulmonary disease (COPD), all free from major comorbid dementing conditions were chosen for the study. The groups were matched for age and education. We found a bimodal distribution of cognitive performance in OSA group, which was therefore divided into two clusters having better (OSAb, n = 35) and worse (OSAw, n = 14) performance on a battery of 10 cognitive indexes. Cognitive performances of OSAb, OSAw, MID, DAT and COPD were compared by discriminant analysis. OSAb performed better than OSAw in all but one test. Deductive thinking and verbal attainment were more severely impaired in OSAw than in COPD patients. Constructive ability, deductive thinking and both verbal attainment and immediate memory were comparably impaired in OSAw and DAT. The mean neuropsychological scores of OSAw and MID were comparable, but 71% of OSAw patients had a distinctive cognitive profile, i.e. a group specific pattern of cognitive dysfunction, according to discriminant analysis. One of four newly diagnosed OSA patients had a severe and distinctive neuropsychological dysfunction mainly involving inductive and deductive thinking, and constructive ability. Some analogy with cognitive pattern of MID suggests that a mainly subcortical damage underlies this dysfunction.