Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation.

BACKGROUND: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. METHODS: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. RESULTS: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. CONCLUSIONS: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

Long-Term Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease: Association between Clinical Phenotypes and Survival.

BACKGROUND: Long-term noninvasive ventilation (LTNIV) is widely used in patients with chronic hypercapnic respiratory failure (CHRF) related to COPD. Prognosis of these patients is however poor and heterogenous. RESEARCH QUESTION: In COPD patients under LTNIV for CHRF, is it possible to identify specific phenotypes which are predictive of probability of pursuing NIV and survival? STUDY DESIGN AND METHODS: A latent class analysis was performed in a COPD population under LTNIV included in a comprehensive database of patients in the Geneva Lake area, to determine clinically relevant phenotypes. The observation period of this subgroup of COPD was extended to allow assessment of survival and/or pursuit of NIV for at least 2 years after inclusion. A logistic regression was conducted to generate an equation accurately attributing an individual patient to a defined phenotype. The identified phenotypes were compared on a series of relevant variables, as well as for probability of pursuing NIV or survival. A competitive risk analysis allowed to distinguish death from other causes of cessation of NIV. RESULTS: Two phenotypes were identified: a "respiratory COPD" profile with very severe airway obstruction, a low or normal body mass index, and a low prevalence of comorbidities and a "systemic COPD" profile of obese COPDs with moderate airway obstruction and a high rate of cardiovascular and metabolic comorbidities. The logistic regression correctly classified 95.7% of patients studied. Probability of pursuing NIV and survival were significantly related to these phenotypes, with a poorer prognosis for "respiratory COPD." Probability of death 5 years after implementing NIV was 22.3% (95% CI: 15.4-32.2) for "systemic COPD" versus 47.2% (37.4-59.6) for "respiratory COPD" (p = 0.001). CONCLUSION: The two distinct phenotypes of COPD under LTNIV for CHRF identified appear to be strongly related to prognosis and require further validation in other cohort studies.

Long-Term Non-invasive Ventilation: Do Patients Aged Over 75 Years Differ From Younger Adults?

Background: Noninvasive ventilation (NIV) is accepted as standard of care for chronic hypercapnic respiratory failure (CHRF) and is being increasingly implemented in older subjects. However, little is known regarding the use of NIV on a long-term basis in the very old. The outcomes of this study were: 1/to report the proportion of patients ≥ 75 years old (elderly) among a large group of long-term NIV users and its trend since 2000; 2/to compare this population to a younger population (<75 years old) under long-term NIV in terms of diagnoses, comorbidities, anthropometric data, technical aspects, adherence to and efficiency of NIV. Methods: In a cross-sectional analysis of a multicenter cohort study on patients with CHRF under NIV, diagnoses, comorbidities, technical aspects, adherence to and efficiency of NIV were compared between patients ≥ 75 and <75 years old (chi-square or Welch Student tests). Results: Of a total of 489 patients under NIV, 151 patients (31%) were ≥ 75 years of age. Comorbidities such as systemic hypertension (86 vs. 60%, p < 0.001), chronic heart failure (30 vs. 18%, p = 0.005), and pulmonary hypertension (25 vs. 14%, p = 0.005) were more frequent in older subjects. In the older group, there was a trend for a higher prevalence of chronic obstructive pulmonary disease (COPD) (46 vs. 36%, p = 0.151) and a lower prevalence of neuromuscular diseases (NMD) (19 vs. 11%, p = 0.151), although not significant. Adherence to and efficacy of NIV were similar in both groups (daily use of ventilator: 437 vs. 419 min, p = 0.76; PaCO2: 5.8 vs. 5.9 kPa, p = 0.968). Unintentional leaks were slightly higher in the older group (1.8 vs. 0.6 L/min, p = 0.018). Conclusions: In this cross-sectional study, one third of the population under NIV was ≥ 75 years old. Markers of efficacy of NIV, and adherence to treatment were similar when compared to younger subjects, confirming the feasibility of long-term NIV in the very old. Health-related quality of life was not assessed in this study and further research is needed to address this issue.

Adaptive Servo-Ventilation: A Comprehensive Descriptive Study in the Geneva Lake Area.

Background: Use of adaptive servo-ventilation (ASV) has been questioned in patients with central sleep apnea (CSA) and chronic heart failure (CHF). This study aims to detail the present use of ASV in clinical practice. Methods: Descriptive, cross-sectional, multicentric study of patients undergoing long term (≥3 months) ASV in the Cantons of Geneva or Vaud (1,288,378 inhabitants) followed by public or private hospitals, private practitioners and/or home care providers. Results: Patients included (458) were mostly male (392; 85.6%), overweight [BMI (median, IQR): 29 kg/m2 (26; 33)], comorbid, with a median age of 71 years (59-77); 84% had been treated by CPAP before starting ASV. Indications for ASV were: emergent sleep apnea (ESA; 337; 73.6%), central sleep apnea (CSA; 108; 23.6%), obstructive sleep apnea (7; 1.5%), and overlap syndrome (6; 1.3%). Origin of CSA was cardiac (n = 30), neurological (n = 26), idiopathic (n = 28), or drug-related (n = 22). Among CSA cases, 60 (56%) patients had an echocardiography within the preceding 12 months; median left ventricular ejection fraction (LVEF) was 62.5% (54-65); 11 (18%) had a LVEF ≤45%. Average daily use of ASV was [mean (SD)] 368 (140) min; 13% used their device <3:30 h. Based on ventilator software, apnea-hypopnea index was normalized in 94% of subjects with data available (94% of 428). Conclusions: Use of ASV has evolved from its original indication (CSA in CHF) to a heterogeneous predominantly male, aged, comorbid, and overweight population with mainly ESA or CSA. CSA in CHF represented only 6.5% of this population. Compliance and correction of respiratory events were satisfactory. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04054570.