Publications by authors named "Jean-Paul Janssens"

147 Publications

Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized control trials.

Respir Res 2021 Jul 23;22(1):209. Epub 2021 Jul 23.

Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Background: In some RCTs comparing triple therapy with dual therapy in COPD, there might be a bias resulting from the use of multiple inhaler devices. This meta-analysis included only RCTs that compared ICS/LABA/LAMA vs. LABA/LAMA or ICS/LABA using a single device.

Methods: We systematically reviewed randomized controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. We searched the PubMed, MEDLINE (OvidSP), EMBASE and Cochrane Library databases to investigate the effect of single-inhaler triple therapy in COPD. The primary end points were the effect of single-inhaler triple therapy compared with single-inhaler dual therapy on all-cause mortality, the risk of acute exacerbation of COPD (AECOPD), and some safety endpoints. The Cochrane Collaboration tool was used to assess the quality of each randomized trial and the risk of bias.

Results: A total of 25,171 patients suffering from COPD were recruited for the 6 studies. This meta-analysis indicated that single-inhaler triple therapy resulted in a significantly lower rate of all-cause mortality than LABA/LAMA FDC (risk ratio, 0.70; 95% CI 0.56-0.88). Single-inhaler triple therapy reduced the risk of exacerbation and prolonged the time to first exacerbation compared with single-inhaler dual therapy. The FEV1 increased significantly more under single-inhaler triple therapy than under ICS/LABA FDC (mean difference, 103.4 ml; 95% CI 64.65-142.15). The risk of pneumonia was, however, significantly higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC (risk ratio, 1.55; 95% CI 1.35-1.80).

Conclusions: This meta-analysis suggests that single-inhaler triple therapy is effective in reducing the risk of death of any cause and of moderate or severe exacerbation in COPD patients. However, the risk of pneumonia is higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC. Trial registration PROSPERO #CRD42020186726.
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http://dx.doi.org/10.1186/s12931-021-01794-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299655PMC
July 2021

Longitudinal Timed Up and Go Assessment in Amyotrophic Lateral Sclerosis: A Pilot Study.

Eur Neurol 2021 Jun 24:1-5. Epub 2021 Jun 24.

Division of Cognitive and Motor Aging, Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, USA.

Progressive loss of walking ability in amyotrophic lateral sclerosis (ALS) has been scarcely studied as a potential predictive factor for survival in motor neuron disease. We aimed to assess the progression of gait decline and its association with mortality in ALS using the Timed Up and Go test (TUG). Patients were followed up prospectively at the Centre for ALS and Related Disorders in Geneva University Hospitals between 2012 and 2016. The TUG was performed at baseline and subsequent evaluations occurred every 3 months. At inclusion, patients were classified as unable to perform the TUG, "slow TUG" (>10.6 s), and "fast TUG" (≤10.6 s). In total, 68 patients with ALS (mean ± SD age: 68.6 ± 11.9 years; 50% female) were included. Baseline TUG was negatively correlated with the total ALSFRS-R score (r = -0.63, p < 0.001). At baseline, ALS patients with bulbar onset performed the TUG faster (9.9 ± 3.7 s) than the non-bulbar ones (17.3 ± 14.9 s, p = 0.008). Thirty of 68 (44%) patients died by the end of the follow-up period. The TUG performance at the first visit did not predict mortality. While we did not find any association with mortality in ALS and gait quantification, the TUG was feasible in a majority of ALS patients, was correlated with functional status, and could be of interest in the follow-up of non-bulbar ALS patients.
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http://dx.doi.org/10.1159/000516772DOI Listing
June 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 Jun 15:1-9. 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
June 2021

REINVENT: ERS International survey on REstrictive thoracic diseases IN long term home noninvasive VENTilation.

ERJ Open Res 2021 Apr 19;7(2). Epub 2021 Apr 19.

Pulmonology and Respiratory Intensive Care Unit, S Donato Hospital, Arezzo, Italy.

Background And Aim: Little is known about the current use of long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases, including chest wall disorders and neuromuscular disorders (NMD). This study aimed to capture the pattern of LTHNIV in patients with restrictive thoracic diseases a web-based international survey.

Methods: The survey involved European Respiratory Society (ERS) Assembly 2.02 (NIV-dedicated group), from October to December 2019.

Results: 166 (22.2%) out of 748 members from 41 countries responded; 80% were physicians, of whom 43% worked in a respiratory intermediate intensive care unit. The ratio of NMD to chest wall disorders was 5:1, with amyotrophic lateral sclerosis the most frequent indication within NMD (78%). The main reason to initiate LTHNIV was diurnal hypercapnia (71%). Quality of life/sleep was the most important goal to achieve. In 25% of cases, clinicians based their choice of the ventilator on patients' feedback. Among NIV modes, spontaneous-timed pressure support ventilation (ST-PSV) was the most frequently prescribed for day- and night-time. Mouthpieces were the preferred daytime NIV interface, whereas oro-nasal masks the first choice overnight. Heated humidification was frequently added to LTHNIV (72%). Single-limb circuits with intentional leaks (79%) were the most frequently prescribed. Follow-up was most often provided in an outpatient setting.

Conclusions: This ERS survey illustrates physicians' practices of LTHNIV in patients with restrictive thoracic diseases. NMD and, specifically, amyotrophic lateral sclerosis were the main indications for LTHNIV. NIV was started mostly because of diurnal hypoventilation with a primary goal of patient-centred benefits. Bi-level ST-PSV and oro-nasal masks were more likely to be chosen for providing NIV. LTHNIV efficacy was assessed mainly in an outpatient setting.
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http://dx.doi.org/10.1183/23120541.00911-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053911PMC
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

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

Recommended Approaches to Minimize Aerosol Dispersion of SARS-CoV-2 During Noninvasive Ventilatory Support Can Cause Ventilator Performance Deterioration: A Benchmark Comparative Study.

Chest 2021 07 2;160(1):175-186. Epub 2021 Mar 2.

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

Background: SARS-CoV-2 aerosolization during noninvasive positive-pressure ventilation may endanger health care professionals. Various circuit setups have been described to reduce virus aerosolization. However, these setups may alter ventilator performance.

Research Question: What are the consequences of the various suggested circuit setups on ventilator efficacy during CPAP and noninvasive ventilation (NIV)?

Study Design And Methods: Eight circuit setups were evaluated on a bench test model that consisted of a three-dimensional printed head and an artificial lung. Setups included a dual-limb circuit with an oronasal mask, a dual-limb circuit with a helmet interface, a single-limb circuit with a passive exhalation valve, three single-limb circuits with custom-made additional leaks, and two single-limb circuits with active exhalation valves. All setups were evaluated during NIV and CPAP. The following variables were recorded: the inspiratory flow preceding triggering of the ventilator, the inspiratory effort required to trigger the ventilator, the triggering delay, the maximal inspiratory pressure delivered by the ventilator, the tidal volume generated to the artificial lung, the total work of breathing, and the pressure-time product needed to trigger the ventilator.

Results: With NIV, the type of circuit setup had a significant impact on inspiratory flow preceding triggering of the ventilator (P < .0001), the inspiratory effort required to trigger the ventilator (P < .0001), the triggering delay (P < .0001), the maximal inspiratory pressure (P < .0001), the tidal volume (P = .0008), the work of breathing (P < .0001), and the pressure-time product needed to trigger the ventilator (P < .0001). Similar differences and consequences were seen with CPAP as well as with the addition of bacterial filters. Best performance was achieved with a dual-limb circuit with an oronasal mask. Worst performance was achieved with a dual-limb circuit with a helmet interface.

Interpretation: Ventilator performance is significantly impacted by the circuit setup. A dual-limb circuit with oronasal mask should be used preferentially.
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http://dx.doi.org/10.1016/j.chest.2021.02.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921720PMC
July 2021

Predictors of mortality in COPD exacerbation cases presenting to the respiratory intensive care unit.

Respir Res 2021 Mar 4;22(1):77. Epub 2021 Mar 4.

Department of Respiratory and Critical Care Medicine, Beijing Hospital, Beijing, China.

Background: Studies report high in-hospital mortality of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) especially for those requiring admission to an intensive care unit. Recognizing factors associated with mortality in these patients could reduce health care costs and improve end-of-life care.

Methods: This retrospective study included AECOPD patients admitted to the respiratory intensive care unit of a tertiary hospital in Beijing from Jan 1, 2011 to Dec 31, 2018. Patients demographic characteristics, blood test results and comorbidities were extracted from the electronic medical record system and compared between survivors and non-survivors.

Results: We finally enrolled 384 AECOPD patients: 44 (11.5%) patients died in hospital and 340 (88.5%) were discharged. The most common comorbidity was respiratory failure (294 (76.6%)), followed by hypertension (214 (55.7%)), coronary heart disease (115 (29.9%)) and chronic heart failure (76 (19.8%)). Multiple logistic regression analysis revealed that independent risk factors associated with in-hospital mortality included lymphocytopenia, leukopenia, chronic heart failure and requirement for invasive mechanical ventilation.

Conclusions: The in-hospital mortality of patients with acute COPD exacerbation requiring RICU admission is high. Lymphocytes < 0.8 × 10/L, leukopenia, requirement for invasive mechanical ventilation, and chronic heart failure were identified as risk factors associated with increased mortality rates.
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http://dx.doi.org/10.1186/s12931-021-01657-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930515PMC
March 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

Prevalence and Risk Factors for COPD at High Altitude: A Large Cross-Sectional Survey of Subjects Living Between 2,100-4,700 m Above Sea Level.

Front Med (Lausanne) 2020 3;7:581763. Epub 2020 Dec 3.

National Clinical Research Center for Respiratory Diseases, Beijing, China.

Four hundred million people live at high altitude worldwide. Prevalence and risk factors for COPD in these populations are poorly documented. We examined the prevalence and risk factors for COPD in residents living at an altitude of 2,100-4,700 m. We performed a cross-sectional survey in Xinjiang and Tibet autonomous region. A multistage stratified sampling procedure was used to select a representative population aged 15 years or older from eight high altitude regions. All participants underwent pre- and post-bronchodilator measurement of forced expiratory volumes. COPD was diagnosed according to 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Between June, 2015 and August 2016, 4,967 subjects were included. Median age was 38.0 years (range: 15-91 years; inter-quartile range: 28-49 years); 51.4% participants were female. Overall prevalence of spirometry-defined COPD was 8.2% (95% CI 7.4-8.9%): 9.3% in male (95% CI 8.2-10.4%), and 7.1% in female (95% CI 6.1-8.2%). By multivariable logistic regression analysis, COPD was significantly associated with being aged ≥40 years (odds ratio: 2.25 [95% CI 1.72-2.95], < 0.0001), exposure to household air pollution (OR: 1.34 [95% CI 1.01-1.79], = 0.043), and a history of tuberculosis (OR: 1.79 [95% CI 1.23-2.61], = 0.030), while living at a higher altitude (OR: 0.45 [95% CI 0.33-0.61], < 0.0001) and having a higher educational level (OR: 0.64 [95% CI 0.43-0.95], = 0.025) were associated with a lower prevalence of COPD. Our results show that the spirometry-defined COPD is a considerable health problem for residents living at high altitudes and COPD prevalence was inversely correlated with altitude. Preventing exposure to household air pollution and reducing the incidence of tuberculosis should be public health priorities for high altitude residents.
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http://dx.doi.org/10.3389/fmed.2020.581763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744817PMC
December 2020

Monitoring of noninvasive ventilation: comparative analysis of different strategies.

Respir Res 2020 Dec 10;21(1):324. Epub 2020 Dec 10.

Department of Pulmonary Medicine and Intensive Care Unit, University Hospital, Dijon, France.

Background: Noninvasive ventilation (NIV) represents an effective treatment for chronic respiratory failure. However, empirically determined NIV settings may not achieve optimal ventilatory support. Therefore, the efficacy of NIV should be systematically monitored. The minimal recommended monitoring strategy includes clinical assessment, arterial blood gases (ABG) and nocturnal transcutaneous pulsed oxygen saturation (SpO). Polysomnography is a theoretical gold standard but is not routinely available in many centers. Simple tools such as transcutaneous capnography (TcPCO) or ventilator built-in software provide reliable informations but their role in NIV monitoring has yet to be defined. The aim of our work was to compare the accuracy of different combinations of tests to assess NIV efficacy.

Methods: This retrospective comparative study evaluated the efficacy of NIV in consecutive patients through four strategies (A, B, C and D) using four different tools in various combinations. These tools included morning ABG, nocturnal SpO, TcPCO and data provided by built-in software via a dedicated module. Strategy A (ABG + nocturnal SpO), B (nocturnal SpO + TcPCO) and C (TcPCO + builtin software) were compared to strategy D, which combined all four tools (NIV was appropriate if all four tools were normal).

Results: NIV was appropriate in only 29 of the 100 included patients. Strategy A considered 53 patients as appropriately ventilated. Strategy B considered 48 patients as appropriately ventilated. Strategy C misclassified only 6 patients with daytime hypercapnia.

Conclusion: Monitoring ABG and nocturnal SpO is not enough to assess NIV efficacy. Combining data from ventilator built-in software and TcPCO seems to represent the best strategy to detect poor NIV efficacy. Trial registration Institutional Review Board of the Société de Pneumologie de Langue Française (CEPRO 2016 Georges).
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http://dx.doi.org/10.1186/s12931-020-01586-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725884PMC
December 2020

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

[Air pollution and its impact on the respiratory system].

Rev Med Suisse 2020 Nov;16(715):2211-2216

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

Epidemiological studies have shown an increased respiratory morbidity and mortality as a consequence of exposure to air pollution. Short term exposure to air pollution is associated with an increased respiratory mortality and exacerbation of respiratory symptoms. Long term exposure to air pollution is associated with a progressive lung function decline as well as the development of chronic pulmonary diseases. In this article, we analyze the impact of major atmospheric pollutants on respiratory health and its impact on COPD, asthma and lung cancer. This review explores the impact of household air pollution on respiratory health as well as the relationship between ambient atmospheric air pollution and physical activity.
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November 2020

[Physiopathology and treatment of cough: an etiological approach].

Rev Med Suisse 2020 Nov;16(715):2204-2210

Service de pneumologie, HUG, 1211 Genève 14.

Chronic cough is a common symptom in the consultation of any general practitioner. It may be idiopathic or reflect a chronic disease. However, cough can become excessive, occurring in response to stimuli that do not usually cause this symptom. This entity is called Cough hypersensitivity syndrome (CHS). Its treatment involves the use of neuromodulator substances that specifically target this hypersensitivity, while maintaining intact the cough reflex, essential for protecting the airways. This review aims to present the current knowledge about the pathophysiology of chronic cough, the initial diagnostic approach that this symptom requires and cough treatments either available or in development.
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November 2020

disseminated infection in an immunocompetent patient without predisposing factors.

BMJ Case Rep 2020 Sep 29;13(9). Epub 2020 Sep 29.

Division of Pulmonology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.

Most infections described involve direct inoculation through skin lesions. We describe the case of a patient without risk factors who presented with an intracranial mass and a pulmonary infection with As are rarely pathogens, there is little knowledge about the optimal treatment and outcome of such infections: what is the best mode of administration, what is the best therapy duration and is surgery always required are some of the unanswered questions. In our patient, surgical removal of the mass associated with a 1-year antimycobacterial therapy led to a full recovery. Even though was rapidly identified in sputum, it was initially considered non-pathogenic and the definitive diagnosis required almost 6 weeks of investigations. New molecular techniques will probably lead to more identifications of in the next few years and a better knowledge of their possible pathogenicity and optimal treatment.
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http://dx.doi.org/10.1136/bcr-2020-235842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526288PMC
September 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

Secondary pulmonary alveolar proteinosis treated by lung transplant: A case report.

Respir Med Case Rep 2020 30;30:101108. Epub 2020 May 30.

Division of Pulmonology, Geneva University Hospitals, 1211, Geneva, Switzerland.

Background: Pulmonary alveolar proteinosis (PAP) is a pulmonary disease characterized by disruption of surfactant homeostasis resulting in its accumulation in the alveoli. PAP is classically classified into three categories (Table 1): 1/primary (or autoimmune) with antibodies targeting the GM-CSF pathway, 2/secondary to another disease, typically a hematologic malignancy, and 3/genetic.

Case-report: A 30 year-old woman received an allogenic hematopoietic stem cell transplantation (HSCT) after treatment for acute myeloid leukemia (AML). Within the first 6 months post HSCT, she developed an ocular, oral, digestive and hepatic graft-versus-host disease associated with a mixed ventilatory defect with a very severe obstructive syndrome and a severe CO diffusion impairment. High resolution computed tomography showed a classical "crazy paving" pattern. Aspect and differential cell count of BAL were normal. All microbiological samples remained culture negative. Histo-pathological analysis of transbronchial biopsies was unremarkable. Because of the severity of the respiratory insufficiency, open-lung biopsy (OBL) could not be performed. Despite multiple immunosuppressive therapies, lung function deteriorated rapidly; the patient also developed an excavated fungal lesion unresponsive to treatment. She underwent a bilateral lung transplant 48 months after HSCT. Histo-pathological analysis of explanted lungs showed obliterative bronchiolitis (OB), diffuse PAP and invasive cavitary pulmonary aspergillosis.

Conclusions: This case illustrates the simultaneous occurrence of OB, PAP and a fungal infection in a 30-year old female patient who underwent HSCT for acute myeloid leukemia (AML). To our knowledge this is the only documented case of PAP associated with OB treated by lung transplantation.
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http://dx.doi.org/10.1016/j.rmcr.2020.101108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276430PMC
May 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

Performances and usefulness of Xpert MTB/RIF assay in low-incidence settings: not that bad?

Eur J Clin Microbiol Infect Dis 2020 Sep 18;39(9):1645-1649. Epub 2020 Apr 18.

Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, CH 1211, Geneva, Switzerland.

Xpert MTB/RIF assay, a real-time PCR assay designed to detect Mycobacterium tuberculosis, has proven sensitive and specific when performed on respiratory samples in a high prevalence setting. However, it was suggested as less accurate in a low-incidence environment. We evaluated the accuracy of the Xpert for the diagnosis of tuberculosis (TB) on pulmonary and extrapulmonary samples in Geneva (Switzerland), where the prevalence of active TB is very low. From March 2009 to February 2013, the Xpert was performed on clinical samples. All specimens were also processed using auramine, AFB staining, and mycobacterial culture with both solid and liquid media. The accuracy of both microscopy and Xpert was determined retrospectively using cultures as the reference method. A total of 732 clinical specimens were processed with the Xpert. The Xpert had a high specificity (97.5%; 95% confidence interval (CI), 95.8-98.5%) and revealed much more sensitive (82.7%; 95% CI, 74.1-89.0%) than microscopy (55.5%; 95% CI, 45.7-64.8%) for the diagnosis of TB, with a high negative predictive value (96.8%; 95% CI, 95.0-98.0%). The advantage of PCR over microscopy was even more pronounced for extrapulmonary specimens (sensitivity of 70% (95% CI, 50.4-84.6%) compared with 23.3% (95% CI, 10.6-42.7%)). Despite the low prevalence of TB in Switzerland, results performance for respiratory samples was similar to that reported in high prevalence countries. The high negative predictive value is clinically helpful in our setting, where pulmonary TB needs to be reasonably ruled out. When considering extrapulmonary samples, microscopy performed poorly compared with Xpert. This study shows that the Xpert remains accurate and useful in a low-incidence setting.
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http://dx.doi.org/10.1007/s10096-020-03887-8DOI Listing
September 2020

Right diaphragmatic palsy as a cause of QRS alternans.

Eur Heart J 2020 06;41(21):2039

Cardiology Service, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.

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http://dx.doi.org/10.1093/eurheartj/ehaa244DOI Listing
June 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

[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

[Screening for latent tuberculosis infection in immunosuppressed patients not infected with HIV].

Rev Med Suisse 2019 Nov;15(671):2105-2108

Service de pneumologie, HUG, 1211 Genève 14.

Screening for latent tuberculosis infection (LTI) is recommended in immunosuppressed patients due to an increased risk of progression from LTI to active tuberculosis. Screening involves indirect immunological tests such as the tuberculin skin test (TST) and the interferon-y release assays (IGRAs). IGRAs seem to show superior performance compared to TST in screening for LTI. However, their use and interpretation in immunosuppressed patients is questionable, particularly because of an increased number of false negative or indeterminate results and a low agreement between tests. Presently, there are no swiss national recommendations for their use in immunosuppressed -patients, except for candidates to anti-TNF treatment.
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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

Identification of Non-Tuberculous Mycobacteria in COPD Patients Undergoing Lung Volume Reduction: More Frequent than Expected?

Respiration 2019 22;98(3):279-280. Epub 2019 Jul 22.

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

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http://dx.doi.org/10.1159/000501697DOI Listing
September 2020

Disadvantaged Early-Life Socioeconomic Circumstances Are Associated With Low Respiratory Function in Older Age.

J Gerontol A Biol Sci Med Sci 2019 06;74(7):1134-1140

Swiss National Center of Competence in Research LIVES: Overcoming Vulnerability: Life Course Perspectives, University of Geneva, Switzerland.

Background: Poor lung function in late life may stem from early-life risk factors, but the epidemiological evidence is inconsistent. We investigated whether individuals who experienced disadvantageous socioeconomic circumstances (SEC) in early life showed lower levels of respiratory function in older age, a steeper decline over time, and whether these relationships were explained by adult-life SEC, body mass index, and physical inactivity in older age.

Methods: We used data from the Survey of Health Ageing and Retirement in Europe (2004-2015). Participants' peak expiratory flow (PEF) was assessed with a mini-Wright peak flow meter at second, fourth, and sixth waves. Confounder-adjusted linear mixed-effect models were used to examine the associations between early-life SEC and PEF in older age. A total of 21,734 adults aged 50-96 years (46,264 observations) were included in the analyses.

Results: Older adults with disadvantaged early-life SEC showed lower levels of PEF compared with those with advantaged early-life SEC. The association between early-life SEC and late-life PEF persisted after adjusting for adult-life SEC, smoking, physical inactivity, and body mass index. PEF declined with age, but the effect of early-life SEC on this decline was not consistent across robustness and sensitivity analyses.

Conclusions: Early life is a sensitive period for respiratory health. Further considering the effect of SEC arising during this period may improve the prevention of chronic respiratory diseases.
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http://dx.doi.org/10.1093/gerona/gly177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330463PMC
June 2019

Framework for patient-ventilator asynchrony during long-term non-invasive ventilation.

Thorax 2019 07 26;74(7):715-717. Epub 2019 Apr 26.

Pneumology Department, Hospital de Sabadell, Corporació Sanitaria Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain.

Episodes of patient-ventilator asynchrony (PVA) occur during acute and chronic non-invasive positive pressure ventilation (NIV). In long-term NIV, description and quantification of PVA is not standardised, thus limiting assessment of its clinical impact. The present report provides a framework for a systematic analysis of polygraphic recordings of patients under NIV for the detection and classification of PVA validated by bench testing. The algorithm described uses two different time windows: rate asynchrony and intracycle asynchrony. This approach should facilitate further studies on prevalence and clinical impact of PVA in long-term NIV.
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http://dx.doi.org/10.1136/thoraxjnl-2018-213022DOI Listing
July 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
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