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.

[Rare Findings in the Workup of Abdominal Pain]. / Seltene Befunde bei der Abklärung von Bauchschmerzen.

Rare Findings in the Workup of Abdominal Pain Abstract. Atypical symptoms such as abdominal discomfort or epigastric pain can be misleading in patients presenting conditions such as obesity, type 2 diabetes, hypertension or ischemic heart disease. In this article we describe two cases of impressively large adrenal masses discovered only several years after the appearance of nonspecific symptoms.

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.

Long-Term Noninvasive Ventilation in the Geneva Lake Area: Indications, Prevalence, and Modalities.

BACKGROUND: Noninvasive ventilation (NIV) is standard of care for chronic hypercapnic respiratory failure, but indications, devices, and ventilatory modes are in constant evolution. RESEARCH QUESTION: To describe changes in prevalence and indications for NIV over a 15-year period; to provide a comprehensive report of characteristics of the population treated (age, comorbidities, and anthropometric data), mode of implementation and follow-up, devices, modes and settings used, physiological data, compliance, and data from ventilator software. STUDY DESIGN AND METHODS: Cross-sectional observational study designed to include all subjects under NIV followed by all structures involved in NIV in the Cantons of Geneva and Vaud (1,288,378 inhabitants). RESULTS: A total of 489 patients under NIV were included. Prevalence increased 2.5-fold since 2000 reaching 38 per 100,000 inhabitants. Median age was 71 years, with 31% being > 75 years of age. Patients had been under NIV for a median of 39 months and had an average of 3 ± 1.8 comorbidities; 55% were obese. COPD (including overlap syndrome) was the most important patient group, followed by obesity hypoventilation syndrome (OHS) (26%). Daytime Paco2 was most often normalized. Adherence to treatment was satisfactory, with 8% only using their device < 3.5 h/d. Bilevel positive pressure ventilators in spontaneous/timed mode was the default mode (86%), with a low use of autotitrating modes. NIV was initiated electively in 50% of the population, in a hospital setting in 82%, and as outpatients in 15%. INTERPRETATION: Use of NIV is increasing rapidly in this area, and the population treated is aging, comorbid, and frequently obese. COPD is presently the leading indication followed by OHS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04054570; URL: www.clinicaltrials.gov.

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.

Immunotherapy-Induced Airway Disease: A New Pattern of Lung Toxicity of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

[Pulmonary embolism: initial management]. / Embolie pulmonaire: prise en charge initiale.

Pulmonary embolism is a frequent disease with well known acquired or hereditary risk factors. The first diagnostic step is to determine a pre-test probability of the disease based on the revised Geneva score. Further work up with D-Dimers, blood gases and ECG, will ascertain the diagnostic of the condition. The prognosis will be better evaluated with BNP and troponine. Negative D-Dimers can rule out pulmonary embolism when pre test probability of the disease is low or intermediate. Radiological work-up includes computed tomographic pulmonary angiography when D-Dimers are positive and when the pre test probability is high, or ventilation/perfusion scan in case of iodine allergy or renal failure. Finally, guidelines will help choosing which patients suffering of pulmonary embolism have to undergo a hematological assessment or oncologic screening.

[Pulmonary emphysema: mechanisms and therapeutic perspectives]. / Emphysème pulmonaire: mécanismes et nouvelles perspectives thérapeutiques.

Emphysema is one of the components of chronic obstructive pulmonary disease beside the bronchial, vascular and systemic parts. The pathogenesis involves an inflammatory process (macrophages, neutrophiles and lymphocytes), but also an imbalance between proteases-anti-proteases and the oxidative stress by the formation of oxygen radicals. On the therapeutic level, these physiopathological pathways are the rational basis to the progressive use of antioxidants (mainly N-acetylcysteine) or, for the moment at an experimental level, of anti-proteases (inhibitors of serine proteases, cysteine proteases and the matrix metalloproteases). To reach the secondary lobule, site of the emphysema, the inhaled future treatments will have to be constituted of small particles, as in cigarette smoke, in order to distribute into the most homogeneous way the affected lung.