Using PaCO2 values to grade obesity-hypoventilation syndrome severity: a retrospective study.

BACKGROUND: To date, an important aspect that has still not been clarified is the assessment of OHS severity. The purpose of this retrospective study was to evaluate whether grading OHS severity according to PaCO2 values may be useful in order to provide a more definite characterization and targeted management of patients. In this regard, baseline anthropometric and sleep polygraphic characteristics, treatment options, and follow up outcomes, were compared between OHS patients with different degree of severity (as assessed according to PaCO2 values). METHODS: Patients were classified into three groups, according to PaCO2 values: 1) mild (46 mmHg ≤ PaCO2 ≤ 50 mmHg), moderate (51 mmHg ≤ PaCO2 ≤ 55 mmHg), severe (PaCO2 ≥ 56 mmHg). Therefore, differences among the groups in terms of baseline anthropometric, and sleep polygraphic characteristics, treatment modalities and follow up outcomes were retrospectively evaluated. RESULTS: Patients with more severe degree of hypercapnia were assessed to have increased BMI and bicarbonate levels, worse diurnal and nocturnal hypoxemia, and a more severe impairment in pulmonary mechanics compared to milder OHS. CPAP responders rate significantly decreased from mild to severe OHS. After follow up, daytime sleepiness (as measure by the ESS), PaO2, and PaCO2 significantly improved with PAP therapy in all three groups. DISCUSSION AND CONCLUSIONS: Classification of OHS severity according to PaCO2 levels may be useful to provide a more defined characterization and, consequently, a more targeted management of OHS patients. Further studies are needed to confirm our findings.

Atrial flutter regression in HIV-associated pulmonary arterial hypertension after treatment with bosentan.

Pulmonary arterial hypertension (PAH) is a rare condition characterized by an increase in pulmonary arterial resistance leading to right heart failure and death. Arrhythmias are a growing problem in PAH; therefore, maintenance of sinus rhythm is considered to be an important treatment aim in these patients. We described the case of a 46-year-old woman with HIV-associated pulmonary arterial hypertension  who developed atrial flutter. After treatment with bosentan, it was observed a significant improvement in clinical and haemodynamic parameters. In addition, the AFL, which had previously persisted to both antiarrhythmic drug therapy and electrical stimulation, and had recurred after transthoracic electrical cardioversion, disappeared  in absence of any antiarrhythmic drug. Though the precise factors responsible for supraventricular arrhythmogenesis are still largely obscure, it is likely that initiation and maintenance of AFL may depend on all the conditions that can lead to increase in right atrial pressure, size, and wall stress, such as PAH. In our case, bosentan reduced both mean pulmonary artery pressure (mPAP) value and right heart chambers pressures. Therefore, it is conceivable that with the anatomical substrate needed for the maintenance of AFL being disappeared, sinus rhythm was restored.

Exercise testing to predict outcome in idiopathic versus associated pulmonary arterial hypertension.

We tested the ability of exercise testing to predict not only survival, but also time to clinical worsening (TTCW) in idiopathic versus associated pulmonary arterial hypertension (PAH). 136 patients with PAH (85 idiopathic and 51 with associated conditions) underwent cardiopulmonary exercise testing and a 6-min walk test. Death or transplantation, and clinical worsening events were recorded. 32 patients died and four had lung transplantation. In a univariate analysis, PAH patients survival was associated with oxygen uptake (V'(O(2))) at peak exercise and at the anaerobic threshold, ventilatory equivalent for carbon dioxide (minute ventilation (V'(E))/carbon dioxide production (V'(CO(2))) at the anaerobic threshold ((at))), V'(E)/V'(CO(2)) slope and distance walked. TTCW was associated with peak V'(O(2)) and V'(O(2),at), V'(E)/V'(CO(2),at), end-tidal carbon dioxide tension measured at the anaerobic threshold, peak oxygen pulse, increase in oxygen pulse and distance walked. In a multivariable analysis, distance walked and V'(E)/V'(CO(2),at) predicted survival, and only peak V'(O(2)) predicted TTCW. The receiver operating characteristic curve-derived cut-off values were 305 m for the 6-min walk distance, 54 for V'(E)/V'(CO(2),at) and 11.6 mL·kg(-1)·min for peak V'(O(2)). In the subgroup with associated PAH, no variable independently predicted either survival or clinical worsening. We conclude that several exercise variables predict survival and clinical stability in idiopathic PAH. Exercise variables are less accurate predictors of outcome in associated PAH.

Early treatment with noninvasive positive pressure ventilation prolongs survival in Amyotrophic Lateral Sclerosis patients with nocturnal respiratory insufficiency.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which rapidly leads to chronic respiratory failure requiring mechanical ventilation. Currently, forced vital capacity (FVC) < 50% is considered as physiologic marker for admitting patients to Noninvasive Positive Pressure Ventilation (NPPV) intervention, although it has been recently shown the median survival of patients with baseline FVC < 75% much shorter than median survival of patients with baseline FVC > 75%, independently by any treatment. AIM: To assess the role of NPPV in improving outcome of ALS, a retrospective analysis was performed to investigate 1 year survival of ALS patients with FVC < 75% and nocturnal respiratory insufficiency, treated with NPPV, compared to a well-matched population of ALS patients, who refused or was intolerant to NPPV. METHODS: We investigated seventy-two consecutive ALS patients who underwent pulmonary function test. Forty-four presented a FVC > 75% and served as control group. Twenty-eight patients presented a FVC < 75% and showed, at polysomnography analysis, nocturnal respiratory insufficiency, requiring NPPV; sixteen were treated with NPPV, while twelve refused or were intolerant. RESULTS: Increased survival rate at 1 year in patients with FVC < 75% treated with NPPV, as compared to those who refused or could not tolerate NPPV (p = 0.02), was observed. The median rate of decline in FVC% was slower in NPPV patients than in patients who did not use NPPV (95% CI: 0.72 to 1.85; p < 0.0001). CONCLUSION: This report demonstrates that early treatment with NPPV prolongs survival and reduces decline of FVC% in ALS.

Exhaled and arterial levels of endothelin-1 are increased and correlate with pulmonary systolic pressure in COPD with pulmonary hypertension.

BACKGROUND: Endothelin-1 (ET-1) and Nitric Oxide (NO) are crucial mediators for establishing pulmonary artery hypertension (PAH). We tested the hypothesis that their imbalance might also occur in COPD patients with PAH. METHODS: The aims of the study were to measure exhaled breath condensate (EBC) and circulating levels of ET-1, as well as exhaled NO (FENO) levels by, respectively, a specific enzyme immunoassay kit, and by chemiluminescence analysis in 3 groups of subjects: COPD with PAH (12), COPD only (36), and healthy individuals (15). In order to evaluate pulmonary-artery systolic pressure (PaPs), all COPD patients underwent Echo-Doppler assessment. RESULTS: Significantly increased exhaled and circulating levels of ET-1 were found in COPD with PAH compared to both COPD (p < 0.0001) only, and healthy controls (p < 0.0001). In COPD with PAH, linear regression analysis showed good correlation between ET-1 in EBC and PaPs (r = 0.621; p = 0.031), and between arterial levels of ET-1 and PaPs (r = 0.648; p = 0.022), while arterial levels of ET-1 inversely correlated with FEV1%, (r = -0.59, p = 0.043), and PaPs negatively correlated to PaO2 (r = -0.618; p = 0.032). Significantly reduced levels of FENO were found in COPD associated with PAH, compared to COPD only (22.92 +/- 11.38 vs.35.07 +/- 17.53 ppb; p = 0.03). Thus, we observed an imbalanced output in the breath between ET-1 and NO, as expression of pulmonary endothelium and epithelium impairment, in COPD with PAH compared to COPD only. Whether this imbalance is an early cause or result of PAH due to COPD is still unknown and deserves further investigations.