Publications by authors named "Dan Adler"

73 Publications

Symptomatic response to CPAP in obstructive sleep apnea versus COPD- obstructive sleep apnea overlap syndrome: Insights from a large national registry.

PLoS One 2021 12;16(8):e0256230. Epub 2021 Aug 12.

Division of Pneumology, Geneva University Hospitals, Geneva, Switzerland.

Background: The symptomatic response to continuous positive airway pressure (CPAP) therapy in COPD-obstructive sleep apnea overlap syndrome (OVS) compared to OSA syndrome (OSA) alone has not been well studied so far. The aim of this study is to explore main differences in the clinical response to CPAP treatment in OVS compared to OSA alone.

Study Design And Methods: Using prospective data from the French National Sleep Apnea Registry, we conducted an observational study among 6320 patients with moderate-to-severe OSA, available spirometry, and at least one follow-up visit under CPAP therapy.

Results: CPAP efficacy measured on the residual apnea-hypopnea index and median adherence were similar between OVS and OSA patients. In both groups, the overall burden of symptoms related to sleep apnea improved with CPAP treatment. In a multivariable model adjusted for age, gender, body mass index, adherence to treatment and residual apnea-hypopnea index, OVS was associated with higher odds for persistent morning headaches (OR: 1.37 [95% CI; 1.04; 1.79]; P = 0.02), morning tiredness (OR: 1.33 [95% CI: 1.12; 1.59]; P<0.01), daytime sleepiness (OR; 1.24 [95% CI: 1.4; 1.46]: P<0.01) and exertional dyspnea (OR: 1.26 [95% CI: 1.00;1.58]; P = 0.04) when compared with OSA alone.

Interpretation: CPAP therapy was effective in normalizing the apnea-hypopnea index and significantly improved OSA-related symptoms, regardless of COPD status. CPAP should be offered to patients with OVS on a trial basis as a significant improvement in OSA-related symptoms can be expected, although the range of response may be less dramatic than in OSA alone.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256230PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360593PMC
August 2021

Cardiac Output Determination in Precapillary Pulmonary Hypertension: A Systematic Review.

Respiration 2021 Jul 13:1-8. Epub 2021 Jul 13.

Pulmonary Hypertension Program, Geneva University Hospitals, Geneva, Switzerland.

Background: Cardiac output determination is essential in precapillary pulmonary hypertension. While direct Fick is the gold standard, thermodilution is commonly used as the reference method. Moving to noninvasive methods would be highly beneficial for patients, avoiding repetitive invasive assessments. This systematic review followed 3 objectives: (1) assessing the validity of indirect Fick and thermodilution in precapillary pulmonary hypertension, (2) assessing the interchangeability of noninvasive cardiac output measurement methods against reference methods in precapillary pulmonary hypertension, and (3) detecting methodological heterogeneity in the included studies.

Methods: We systematically reviewed the literature using medical databases and following PRISMA guidelines. We included articles comparing an invasive or noninvasive cardiac output measurement method with thermodilution or direct Fick in precapillary pulmonary hypertension patients. Cutoffs of limits of agreement and percentage error derived from the Bland and Altman graph were used to accept interchangeability. To study methodological heterogeneity, we extracted 9 quality criteria from all studies.

Results: Eleven studies were included. None reached the suggested interchangeability criteria. The median number of the 9 assessed quality criteria was 2 with interquartile range (0-4).

Conclusions: Further studies evaluating the reliability of thermodilution and the consequences of its use in precapillary pulmonary hypertension patients are necessary. No evidence supports the use of indirect Fick in precapillary pulmonary hypertension. The studied noninvasive methods could not be considered interchangeable with invasive methods. A robust methodology should be used to draw sensible conclusions.
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http://dx.doi.org/10.1159/000517084DOI Listing
July 2021

Impact of Confinement in Patients under Long-Term Noninvasive Ventilation during the First Wave of the SARS-CoV-2 Pandemic: A Remarkable Resilience.

Respiration 2021 15;100(9):909-917. Epub 2021 Jun 15.

Division of Pulmonary Diseases, Geneva University Hospitals, Geneva, Switzerland.

Background: During the first wave of the SARS-CoV-2 pandemic in Switzerland, confinement was imposed to limit transmission and protect vulnerable persons. These measures may have had a negative impact on perceived quality of care and symptoms in patients with chronic disorders.

Objectives: To determine whether patients under long-term home noninvasive ventilation (LTHNIV) for chronic respiratory failure (CRF) were negatively affected by the 56-day confinement (March-April 2020).

Methods: A questionnaire-based survey exploring mood disturbances (HAD), symptom scores related to NIV (S3-NIV), and perception of health-care providers during confinement was sent to all patients under LTHNIV followed up by our center. Symptom scores and data obtained by ventilator software were compared between confinement and the 56 days prior to confinement.

Results: Of a total of 100 eligible patients, 66 were included (median age: 66 years [IQR: 53-74]): 35 (53%) with restrictive lung disorders, 20 (30%) with OHS or SRBD, and 11 (17%) with COPD or overlap syndrome. Prevalence of anxiety (n = 7; 11%) and depressive (n = 2; 3%) disorders was remarkably low. Symptom scores were slightly higher during confinement although this difference was not clinically relevant. Technical data regarding ventilation, including compliance, did not change. Patients complained of isolation and lack of social contact. They felt supported by their relatives and caregivers but complained of the lack of regular contact and information by health-care professionals.

Conclusions: Patients under LTHNIV for CRF showed a remarkable resilience during the SARS-CoV-2 confinement period. Comments provided may be helpful for managing similar future health-care crises.
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http://dx.doi.org/10.1159/000516327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339039PMC
June 2021

Role of Intermediate Care Unit Admission and Noninvasive Respiratory Support during the COVID-19 Pandemic: A Retrospective Cohort Study.

Respiration 2021 21;100(8):786-793. Epub 2021 May 21.

Department of Medicine, Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland.

Background: The COVID-19 pandemic has led to shortage of intensive care unit (ICU) capacity. We developed a triage strategy including noninvasive respiratory support and admission to the intermediate care unit (IMCU). ICU admission was restricted to patients requiring invasive ventilation.

Objectives: The aim of this study is to describe the characteristics and outcomes of patients admitted to the IMCU.

Method: Retrospective cohort including consecutive patients admitted between March 28 and April 27, 2020. The primary outcome was the proportion of patients with severe hypoxemic respiratory failure avoiding ICU admission. Secondary outcomes included the rate of emergency intubation, 28-day mortality, and predictors of ICU admission.

Results: One hundred fifty-seven patients with COVID-19-associated pneumonia were admitted to the IMCU. Among the 85 patients admitted for worsening respiratory failure, 52/85 (61%) avoided ICU admission. In multivariate analysis, PaO2/FiO2 (OR 0.98; 95% CI: 0.96-0.99) and BMI (OR 0.88; 95% CI: 0.78-0.98) were significantly associated with ICU admission. No death or emergency intubation occurred in the IMCU.

Conclusions: IMCU admission including standardized triage criteria, self-proning, and noninvasive respiratory support prevents ICU admission for a large proportion of patients with COVID-19 hypoxemic respiratory failure. In the context of the COVID-19 pandemic, IMCUs may play an important role in preserving ICU capacity by avoiding ICU admission for patients with worsening respiratory failure and allowing early discharge of ICU patients.
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http://dx.doi.org/10.1159/000516329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247832PMC
August 2021

Does Endothelial Vulnerability in OSA Syndrome Promote COVID-19 Encephalopathy?

Chest 2021 08 27;160(2):e161-e164. Epub 2021 Apr 27.

Department of Neurosciences, Division of Neurology, Geneva University Hospitals, Geneva, Switzerland; Department of Neurology, Division of Cognitive and Motor Aging, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY.

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http://dx.doi.org/10.1016/j.chest.2021.04.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076771PMC
August 2021

[Pathophysiology of COVID-19 related happy hypoxemia].

Rev Med Suisse 2021 Apr;17(736):831-834

Service de pneumologie, Département des spécialités de médecine, HUG, 1211 Genève 14.

A significative proportion of patients with pulmonary-related COVID-19 initially present with « silent » or « happy » hypoxemia, a term denoting an absence of dyspnea or other respiratory distress symptoms in face of profound hypoxemia. COVID-19 is a multisystemic disease characterized by the diffusion of SARS-COV-2 through the blood and a widespread secondary immune response. Most of the organs are involved, including the brain and this translates into the development of acute encephalopathy and other complications. Silent hypoxemia and the consequent "vanishing dyspnea" represent a loss of warning signal and may be associated with a rapid clinical worsening and a fatal outcome. In this article, we will describe the physiological basis of ventilation and we will elucidate the different pathophysiological mechanisms underlying the phenomenon of silent hypoxemia in COVID-19.
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April 2021

Early advance care planning in amyotrophic lateral sclerosis patients: results of a systematic intervention by a palliative care team in a multidisciplinary management programme - a 4-year cohort study.

Swiss Med Wkly 2021 Mar 18;151:w20484. Epub 2021 Mar 18.

Palliative Care Consultation, Division of Palliative Medicine, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland / Unit for Development and Research in Medical Education (UDREM), Faculty of Medicine, University of Geneva, Switzerland.

Introduction: Although recommended, the implementation of early advance care planning is suboptimal in amyotrophic lateral sclerosis (ALS) patients. Barriers to advance care planning include healthcare professionals’ and patients’ reluctance, and uncertainty about the right time to initiate a discussion.

Aim Of The Study: To determine how often advance care planning was initiated, and the content of the discussion in a first routine palliative care consultation integrated within a multidisciplinary management programme.

Methods: Between June 2012 and September 2016, a prospective cohort study was conducted in Geneva University Hospitals. Sixty-eight patients were seen every 3 months for a 1-day clinical evaluation in a day care centre.

Results: The patients’ mean ± standard deviation age was 68.6 ± 11.9 years, 50% were women. Four patients were excluded because of dementia. Advance care planning was initiated with 49 (77%) patients in the first palliative care consultation. Interventions most often addressed were cardiopulmonary resuscitation (49%), intubation and tracheostomy (47%) and palliative sedation (36.7%). Assisted suicide was discussed with 16 patients (36.6%). Functional disability was the only factor associated with initiation of advance care planning. Nearly half of the patients wrote advance directives (45%) or designated a healthcare surrogate (41%). Bulbar onset, functional disability and noninvasive ventilation were not associated with the completion of advance directives.

Conclusion: Early initiation of advance care planning is feasible in most ALS patients during a routine consultation, and relevant treatment issues can be discussed. All ALS patients should be offered the opportunity to write advance directives as completion was not associated with disease severity. .
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http://dx.doi.org/10.4414/smw.2021.20484DOI Listing
March 2021

CPAP Therapy Termination Rates by OSA Phenotype: A French Nationwide Database Analysis.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

SEMEIA, 75010 Paris, France.

The nationwide claims data lake for sleep apnoea (ALASKA)-real-life data for understanding and increasing obstructive sleep apnea (OSA) quality of care study-investigated long-term continuous positive airway pressure (CPAP) termination rates, focusing on the contribution of comorbidities. The French national health insurance reimbursement system data for new CPAP users aged ≥18 years were analyzed. Innovative algorithms were used to determine the presence of specific comorbidities (hypertension, diabetes and chronic obstructive pulmonary disease (COPD)). Therapy termination was defined as cessation of CPAP reimbursements. A total of 480,000 patients were included (mean age 59.3 ± 13.6 years, 65.4% male). An amount of 50.7, 24.4 and 4.3% of patients, respectively, had hypertension, diabetes and COPD. Overall CPAP termination rates after 1, 2 and 3 years were 23.1, 37.1 and 47.7%, respectively. On multivariable analysis, age categories, female sex (1.09 (1.08-1.10) and COPD (1.12 (1.10-1.13)) and diabetes (1.18 (1.16-1.19)) were significantly associated with higher CPAP termination risk; patients with hypertension were more likely to continue using CPAP (hazard ratio 0.96 (95% confidence interval 0.95-0.97)). Therapy termination rates were highest in younger or older patients with ≥1 comorbidity. Comorbidities have an important influence on long-term CPAP continuation in patients with OSA.
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http://dx.doi.org/10.3390/jcm10050936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957656PMC
March 2021

Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.

ERJ Open Res 2021 Jan 8;7(1). Epub 2021 Mar 8.

Division of Lung Diseases, Geneva University Hospitals, Geneva, Switzerland.

Rationale And Objectives: Prone positioning as a complement to oxygen therapy to treat hypoxaemia in coronavirus disease 2019 (COVID-19) pneumonia in spontaneously breathing patients has been widely adopted, despite a lack of evidence for its benefit. We tested the hypothesis that a simple incentive to self-prone for a maximum of 12 h per day would decrease oxygen needs in patients admitted to the ward for COVID-19 pneumonia on low-flow oxygen therapy.

Methods: 27 patients with confirmed COVID-19 pneumonia admitted to Geneva University Hospitals were included in the study. 10 patients were randomised to self-prone positioning and 17 to usual care.

Measurements And Main Results: Oxygen needs assessed by oxygen flow on nasal cannula at inclusion were similar between groups. 24 h after starting the intervention, the median (interquartile range (IQR)) oxygen flow was 1.0 (0.1-2.9) L·min in the prone position group and 2.0 (0.5-3.0) L·min in the control group (p=0.507). Median (IQR) oxygen saturation/fraction of inspired oxygen ratio was 390 (300-432) in the prone position group and 336 (294-422) in the control group (p=0.633). One patient from the intervention group who did not self-prone was transferred to the high-dependency unit. Self-prone positioning was easy to implement. The intervention was well tolerated and only mild side-effects were reported.

Conclusions: Self-prone positioning in patients with COVID-19 pneumonia requiring low-flow oxygen therapy resulted in a clinically meaningful reduction of oxygen flow, but without reaching statistical significance.
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http://dx.doi.org/10.1183/23120541.00692-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869594PMC
January 2021

[Novel therapies in respiratory management].

Rev Med Suisse 2021 Jan;17(723):209-213

Service de pneumologie, Département des spécialités de médecine, HUG, 1211 Genève 14.

In this review of the recent medical literature, we have identified 4 topics of interest for the readers of Revue Médicale Suisse. Use of antifibrotic drugs in interstitial lung diseases will soon be extended to a phenotype labeled « progressive fibrosing interstitial lung disease » (PF-ILD). While awaiting for evidence-based treatment, consensual recommendations for a treatment algorithm in pulmonary sarcoidosis has been published. New guidance for non-invasive ventilation in COPD and obesity-hypoventilation syndrome are available in Switzerland and are in line with international recommendations. New treatments targeting CFTR protein activity have become available and could become a therapeutic option for up to 85% of cystic fibrosis patients in Switzerland.
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January 2021

Long-Term Mechanical Ventilation: Recommendations of the Swiss Society of Pulmonology.

Respiration 2020 Dec 10:1-36. Epub 2020 Dec 10.

Division of Pulmonary Diseases, Geneva University Hospitals, Geneva, Switzerland.

Long-term mechanical ventilation is a well-established treatment for chronic hypercapnic respiratory failure (CHRF). It is aimed at improving CHRF-related symptoms, health-related quality of life, survival, and decreasing hospital admissions. In Switzerland, long-term mechanical ventilation has been increasingly used since the 1980s in hospital and home care settings. Over the years, its application has considerably expanded with accumulating evidence of beneficial effects in a broad range of conditions associated with CHRF. Most frequent indications for long-term mechanical ventilation are chronic obstructive pulmonary disease, obesity hypoventilation syndrome, neuromuscular and chest wall diseases. In the current consensus document, the Special Interest Group of the Swiss Society of Pulmonology reviews the most recent scientific literature on long-term mechanical ventilation and provides recommendations adapted to the particular setting of the Swiss healthcare system with a focus on the practice of non-invasive and invasive home ventilation in adults.
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http://dx.doi.org/10.1159/000510086DOI Listing
December 2020

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

Front Med (Lausanne) 2020 11;7:556218. Epub 2020 Nov 11.

Division of Pulmonary Diseases, Geneva University Hospitals (HUG), Geneva, Switzerland.

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. 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). Of a total of 489 patients under NIV, 151 patients (31%) were ≥ 75 years of age. Comorbidities such as systemic hypertension (86 vs. 60%, < 0.001), chronic heart failure (30 vs. 18%, = 0.005), and pulmonary hypertension (25 vs. 14%, = 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%, = 0.151) and a lower prevalence of neuromuscular diseases (NMD) (19 vs. 11%, = 0.151), although not significant. Adherence to and efficacy of NIV were similar in both groups (daily use of ventilator: 437 vs. 419 min, = 0.76; PaCO: 5.8 vs. 5.9 kPa, = 0.968). Unintentional leaks were slightly higher in the older group (1.8 vs. 0.6 L/min, = 0.018). 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.
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http://dx.doi.org/10.3389/fmed.2020.556218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686650PMC
November 2020

[Diagnostic approach to chronic dyspnea in adults].

Rev Med Suisse 2020 Nov;16(715):2198-2203

Service de Pneumologie, HUG, 1211 Genève 14.

Dyspnea is a symptom resulting from a complex interaction between multiple mechanisms that are not fully understood to this day. Chronic dyspnea is defined as dyspnea lasting more than one month and this symptom is commonly seen in primary care. Cardio-respiratory pathologies account for approximately 85 % of all cases of dyspnea. Dyspnea significantly impacts the quality of life of the affected patients and is a good predictor of morbidity and mortality. Chronic dyspnea is challenging, especially when the etiology is unclear. Performing pulmonary function tests (PFTs) and a cardiopulmonary exercise test (CPET) allows to better understand the pathophysiology of the dyspnea in order to guide the diagnosis.
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November 2020

Comorbidities and Readmissions in Survivors of Acute Hypercapnic Respiratory Failure.

Semin Respir Crit Care Med 2020 12 3;41(6):806-816. Epub 2020 Aug 3.

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.

Chronic obstructive pulmonary disease (COPD) is defined by chronic airflow obstruction, but is presently considered as a complex, heterogeneous, and multicomponent disease in which comorbidities and extrapulmonary manifestations make important contributions to disease expression. COPD-related hospital readmission. In particular frequent intensive care unit (ICU) readmissions for exacerbations represent a major challenge and place a high burden on patient outcomes and health-related quality of life, as well as on the healthcare system.In this narrative review, we first address major and often undiagnosed comorbidities associated with COPD that could have an impact on hospital readmission after an index ICU admission for acute hypercapnic respiratory failure. Some guidance for treatment is discussed. Second, we present predictors of hospital and ICU readmission and discuss various strategies to reduce such events.There is a strong rationale to detect and treat major comorbidities early after index ICU admission for acute hypercapnic respiratory failure. It still remains unclear, however, if a comprehensive and holistic approach to comorbidities in frail patients surviving hypercapnic respiratory failure can efficiently reduce the readmission rate.
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http://dx.doi.org/10.1055/s-0040-1710074DOI Listing
December 2020

Clinical presentation and comorbidities of obstructive sleep apnea-COPD overlap syndrome.

PLoS One 2020 9;15(7):e0235331. Epub 2020 Jul 9.

Division of Pneumology, Geneva University Hospitals, Geneva, Switzerland.

Background: More advanced knowledge is needed on how COPD alters the clinical presentation of obstructive sleep apnea (OSA) and how the association of both diseases, known as 'overlap syndrome' (OVS), impacts on cardiovascular health.

Objective: To investigate differences between patients with OVS and those with moderate-to-severe OSA alone.

Methods: A cross-sectional study conducted in the French National Sleep Apnea Registry between January 1997 and January 2017. Univariable and multivariable logistic regression models were used to compare OVS versus OSA alone on symptoms and cardiovascular health.

Results: 46,786 patients had moderate-to-severe OSA. Valid spirometry was available for 16,466 patients: 14,368 (87%) had moderate-to-severe OSA alone and 2098 (13%) had OVS. A lower proportion of OVS patients complained of snoring, morning headaches and excessive daytime sleepiness compared to OSA alone (median Epworth Sleepiness Scale score: 9 [interquartile range (IQR) 6-13] versus 10 (IQR 6-13), respectively; P <0.02). Similarly, a lower proportion of OVS patients (35.6% versus 39.4%, respectively; P <0.01) experienced sleepiness while driving. In contrast, 63.5% of the OVS population experienced nocturia compared to 58.0% of the OSA population (P<0.01). Apnea hypopnea index (36 [25; 52] vs 33.1 [23.3; 50]), oxygen desaturation index (28 [15; 48] vs 25.2 [14; 45]) and mean nocturnal SaO2 (92 [90; 93.8] vs 93 [91.3; 94]) were significantly more altered in the OVS group. Associated COPD had no effect on the prevalence of hypertension and stroke. After controlling for main confounders, COPD severity was associated in a dose-response relationship with a higher prevalence of coronary heart disease, heart failure and peripheral arteriopathy.

Conclusions: In adults with moderate-to-severe OSA, OVS was minimally symptomatic, but exhibited higher odds for prevalent coronary heart disease, heart failure and peripheral arteriopathy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235331PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347183PMC
September 2020

Multidisciplinary care in amyotrophic lateral sclerosis: a 4-year longitudinal observational study.

Swiss Med Wkly 2020 Jun 9;150:w20258. Epub 2020 Jun 9.

Division of Pulmonary Diseases, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland / Faculty of Medicine, University of Geneva, Switzerland.

Over a four-year period, ALS patients complied with the modalities of the multidisciplinary management follow-up without any drop-outs. The multidisciplinary management structure also contributes to increasing the experience and knowledge of the clinicians involved in managing patients suffering from this rare disease.
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http://dx.doi.org/10.4414/smw.2020.20258DOI Listing
June 2020

Gait speed is associated with death or readmission among patients surviving acute hypercapnic respiratory failure.

BMJ Open Respir Res 2020 06;7(1)

Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland.

Objectives: Death or hospital readmission are frequent among patients surviving acute hypercapnic respiratory failure (AHRF). Severity scores are not valid to predict death or readmission after AHRF. Gait speed, a simple functional parameter, has been associated with hospital admission and death in the general population. The purpose of this study is to highlight an association between gait speed at hospital discharge and death or readmission among AHRF survivors.

Design: Secondary analysis of a prospective cohort study.

Settings: Single Swiss tertiary hospital, pulmonary division.

Participants: Patients were prospectively recruited to form a cohort of patients surviving AHRF in the intensive care unit between January 2012 and May 2015.

Outcome Measure: Gait speed was derived from a 6 min walking test (6MWT) before hospital discharge. All predictive variables were prospectively collected. Death or hospital readmission were recorded for 6 months. Univariate and multivariate analyses were performed to evaluate the association between predictive variables and death or hospital readmission.

Results: 71 patients performed a 6MWT. 34/71 (48%) patients died or were readmitted to the hospital during the observation period. Median gait speed was 0.7 (IQR 0.3-1.0) m/s. At 6 months, 66% (25/38) of slow walkers (gait speed <0.7 m/s) and 27% (9/33) of non-slow walkers died or were readmitted to the hospital (p=0.002). In univariate analysis, gait speed was associated with death or readmission (HR 0.41; 95% CI 0.19 to 0.90, p=0.025). In a multivariate model adjusted for age, gender, body mass index, forced expired volume, heart failure and home mechanical ventilation, gait speed remained the only variable associated with death or readmission (multivariate HR: 0.35; 95% CI 0.14 to 0.88, p=0.025).

Conclusion: This study suggests that a simple functional parameter such as gait speed is associated with death or hospital readmission in patients surviving AHRF.

Trial Registration Number: NCT02111876.
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http://dx.doi.org/10.1136/bmjresp-2019-000542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304813PMC
June 2020

Dyspnea: The vanished warning symptom of COVID-19 pneumonia.

J Med Virol 2020 11 29;92(11):2272-2273. Epub 2020 Jun 29.

Division of Pulmonary Diseases, Geneva University Hospitals and Faculty of Medicine and University of Geneva, Geneva, Switzerland.

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http://dx.doi.org/10.1002/jmv.26172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307122PMC
November 2020

Hypoxemia in COVID-19; Comment on: "The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients".

J Med Virol 2020 10 27;92(10):1705-1706. Epub 2020 Jul 27.

Service of Internal Medicine, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.

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http://dx.doi.org/10.1002/jmv.26020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276823PMC
October 2020

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

Front Med (Lausanne) 2020 3;7:105. Epub 2020 Apr 3.

Faculty of Medicine, University of Geneva, Geneva, Switzerland.

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. 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. Patients included (458) were mostly male (392; 85.6%), overweight [BMI (median, IQR): 29 kg/m (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 ( = 30), neurological ( = 26), idiopathic ( = 28), or drug-related ( = 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). 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. www.ClinicalTrials.gov, identifier: NCT04054570.
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http://dx.doi.org/10.3389/fmed.2020.00105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145945PMC
April 2020

Experimental dyspnoea interferes with locomotion and cognition: a randomised trial.

Eur Respir J 2020 08 6;56(2). Epub 2020 Aug 6.

Division of Pulmonary Diseases, Geneva University Hospitals, Geneva, Switzerland

Background: Chronic respiratory diseases are associated with cognitive dysfunction, but whether dyspnoea by itself negatively impacts on cognition has not been demonstrated. Cortical networks engaged in subjects experiencing dyspnoea are also activated during other tasks that require cognitive input and this may provoke a negative impact through interference with each other.

Methods: This randomised, crossover trial investigated whether experimentally-induced dyspnoea would negatively impact on locomotion and cognitive function among 40 healthy adults. Crossover conditions were unloaded breathing or loaded breathing using an inspiratory threshold load. To evaluate locomotion, participants were assessed by the Timed Up and Go (TUG) test. Cognitive function was assessed by categorical and phonemic verbal fluency tests, the Trail Making Tests (TMTs) A and B (executive function), the CODE test from the Wechsler Adult Intelligence Scale (WAIS)-IV (processing speed) and by direct and indirect digit span (working memory).

Results: The mean time difference to perform the TUG test between unloaded and loaded breathing was -0.752 s (95% CI -1.012 to -0.492 s) (p<0.001). Executive function, processing speed and working memory performed better during unloaded breathing, particularly for subjects starting first with the loaded breathing condition.

Conclusion: Our data suggest that respiratory threshold loading to elicit dyspnoea had a major impact on locomotion and cognitive function in healthy adults.
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http://dx.doi.org/10.1183/13993003.00054-2020DOI Listing
August 2020

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

Chest 2020 07 31;158(1):279-291. Epub 2020 Mar 31.

Division of Pulmonary Diseases, Geneva University Hospitals (HUG), Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address:

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 Paco 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.
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http://dx.doi.org/10.1016/j.chest.2020.02.064DOI Listing
July 2020

Mechanisms of the breathing contribution to bodily self-consciousness in healthy humans: Lessons from machine-assisted breathing?

Psychophysiology 2020 08 12;57(8):e13564. Epub 2020 Mar 12.

Laboratory of Cognitive Neuroscience, Center for Neuroprosthetics & Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Geneva, Switzerland.

Previous studies investigated bodily self-consciousness (BSC) by experimentally exposing subjects to multisensory conflicts (i.e., visuo-tactile, audio-tactile, visuo-cardiac) in virtual reality (VR) that involve the participant's torso in a paradigm known as the full-body illusion (FBI). Using a modified FBI paradigm, we found that synchrony of visuo-respiratory stimulation (i.e., a flashing outline surrounding an avatar in VR; the flash intensity depending on breathing), is also able to modulate BSC by increasing self-location and breathing agency toward the virtual body. Our aim was to investigate such visuo-respiratory effects and determine whether respiratory motor commands contributes to BSC, using non-invasive mechanical ventilation (i.e., machine-delivered breathing). Seventeen healthy participants took part in a visuo-respiratory FBI paradigm and performed the FBI during two breathing conditions: (a) "active breathing" (i.e., participants actively initiate machine-delivered breaths) and (b) "passive breathing" (i.e., breaths' timing was determined by the machine). Respiration rate, tidal volume, and their variability were recorded. In line with previous results, participants experienced subjective changes in self-location, breathing agency, and self-identification toward the avatar's body, when presented with synchronous visuo-respiratory stimulation. Moreover, drift in self-location was reduced and tidal volume variability were increased by asynchronous visuo-respiratory stimulations. Such effects were not modulated by breathing control manipulations. Our results extend previous FBI findings showing that visuo-respiratory stimulation affects BSC, independently from breathing motor command initiation. Also, variability of respiratory parameters was influenced by visuo-respiratory feedback and might reduce breathing discomfort. Further exploration of such findings might inform the development of respiratory therapeutic tools using VR in patients.
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http://dx.doi.org/10.1111/psyp.13564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507190PMC
August 2020

[Pulmonary medicine: asthma, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis].

Rev Med Suisse 2020 Jan;16(676-7):81-86

Service de pneumologie, Département de médecine, HUG, 1211 Genève 14.

Important changes have been proposed by expert groups for the management of mild asthma and chronic obstructive pulmonary disease (COPD): for safety reasons, short-acting beta-2 agonists (SABA) are no longer recommended as « reliever therapy » in mild asthma, and should be replaced by symptom-driven inhaled corticosteroids, alone or combined with a beta-2 agonist ; for COPD patients recommendations as to use of inhaled corticosteroids have been redefined. New therapeutic options for idiopathic pulmonary fibrosis are being evaluated: recombinant human pentraxin 2 may become a new therapeutic option among the existing specific treatments (pirfenidone, nintedanib). These novelties are discussed in this review of the recent medical literature.
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January 2020

[Overlap syndrome in chronic obstructive pulmonary disease patient].

Rev Med Suisse 2019 Nov;15(671):2087-2089

Service de pneumologie, Département de médecine, HUG, 1211 Genève 14.

Overlap syndrome (OVS) is defined by the co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in a same patient. This condition is associated with increased mortality and a higher risk of respiratory exacerbation, compared to patients with COPD or OSA alone. Nocturnal positive PAP treatment is effective to mitigate the additional risk related to OSA. Identification of OVS is a major challenge for clinicians because of the many phenotypes of OVS patients, with atypical OSA presentation, whose sleep quality is already impacted by COPD itself. Dedicated prospective studies are mandatory to improve our understanding of OVS patients and to optimize their medical care.
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November 2019

Predicting respiratory failure in amyotrophic lateral sclerosis: still a long way to go.

Eur Respir J 2019 Aug 1;54(2). Epub 2019 Aug 1.

Division of Pulmonary Diseases, Dept of Medicine, Geneva University Hospitals, Geneva, Switzerland.

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http://dx.doi.org/10.1183/13993003.01065-2019DOI Listing
August 2019

Assessing Inspiratory Muscle Strength for Early Detection of Respiratory Failure in Motor Neuron Disease: Should We Use MIP, SNIP, or Both?

Respiration 2019;98(2):114-124. Epub 2019 Apr 24.

Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland.

Background: Motor neuron disease (MND) invariably impacts on inspiratory muscle strength leading to respiratory failure. Regular assessment of sniff nasal inspiratory pressure (SNIP) and/or maximal mouth inspiratory pressure (MIP) contributes to early detection of a requirement for ventilatory support.

Objectives: The aim of this study was to compare the feasibility, agreement, and performance of both tests in MND.

Methods: Patients with MND followed by a multidisciplinary consultation were prospectively included. Pulmonary follow-up included forced expiratory volumes, vital capacity (VC) seated and supine, MIP, SNIP, pulse oximetry, and daytime arterial blood gases.

Results: A total of 61 patients were included. SNIP and MIP could not be performed in 14 (21%) subjects; 74% of the subjects showed a decrease in MIP or SNIP at inclusion versus 31% for VC. Correlation between MIP and SNIP (Pearson's rho: 0.68, p < 0.001) was moderate, with a non-significant bias in favor of SNIP (3.6 cm H2O) and wide limits of agreement (-34 to 41 cm H2O). Results were similar in "bulbar" versus "non-bulbar" patients. At different proposed cut-off values for identifying patients at risk of respiratory failure, the agreement between MIP and SNIP (64-79%) and kappa values (0.29-0.53) was moderate.

Conclusions: MIP and SNIP were equally feasible. There was no significant bias in favor of either test, but a considerable disparity in results between tests, suggesting that use of both tests is warranted to screen for early detection of patients at risk of respiratory failure and avoid over diagnoses. SNIP, MIP, and VC all follow a relatively linear downhill course with a steeper slope for "bulbar" versus "non-bulbar" patients.
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http://dx.doi.org/10.1159/000498972DOI Listing
September 2020

Emphysema quantification using hybrid versus model-based generations of iterative reconstruction: SAFIRE versus ADMIRE.

Medicine (Baltimore) 2019 Feb;98(7):e14450

Diagnostic Department, Division of Radiology.

To compare 2 incompatible generations of iterative reconstructions from the same raw dataset based on automatic emphysema quantification and noise reduction: a hybrid algorithm called sinogram affirmed iterative reconstruction (SAFIRE) versus a model-based algorithm called advanced modeled iterative reconstruction (ADMIRE).Raw datasets of 40 non-contrast thoracic computed tomography scanners obtained from a single acquisition on a SOMATOM Definition Flash unit (Siemens Healthcare, Forchheim) were reconstructed with 3 levels of SAFIRE and ADMIRE algorithms resulting in a total of 240 datasets. Emphysema index (EI) and image noise were compared using repeated analysis of variance (ANOVA) analysis with a P value <.05 considered statistically significant.EI and image noise were stable between both generations of IR when reconstructed with the same level (P ≥0.31 and P ≥0.06, respectively).SAFIRE and ADMIRE perform equally in terms of emphysema quantification and noise reduction.
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http://dx.doi.org/10.1097/MD.0000000000014450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408015PMC
February 2019

[Transbronchial cryobiopsies : a minimally invasive tool for the diagnosis of interstitial lung disease].

Rev Med Suisse 2018 Nov;14(627):2079-2083

Service de pneumologie, Département des spécialités de médecine, HUG, 1211 Genève 14.

The diagnosis of interstitial lung disease (ILD) is challenging and relies on a multidisciplinary discussion involving clinical, radiological and sometimes histological features. Bronchoscopic lung cryobiopsies have emerged as a new minimally invasive method of lung sampling and an alternative to surgical lung biopsies. A good diagnostic performance and excellent safety profile make it an interesting and worthful procedure which could decrease the number of patients without proper diagnosis and treatment. There is a need for further studies to standardize the technique in expert centers and to establish its role in the diagnostic work-up of ILD.
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November 2018

[COPD and cognitive impairment].

Rev Med Suisse 2018 Nov;14(627):2066-2069

Service de pneumologie, HUG, 1211 Genève 14.

Patients with chronic respiratory failure, especially COPD, suffer from a multi-systemic disease with organic, behavioral and social consequences that impact largely beyond the respiratory system. Cognitive impairment is associated with decreased quality of life and increased mortality in the general population, but remains underestimated and poorly studied in chronic respiratory diseases despite their increased prevalence. However, there is growing interest in research on the association between cognitive impairment and chronic respiratory diseases. Different risk factors, some modifiable, could contribute to the early development of cognitive disorders in this population. Patients with cognitive impairment need appropriate care to promote adherence to the therapeutic project. Respiratory rehabilitation, as a multimodal intervention, seems to have a positive effect on cognitive functions.
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November 2018
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