Comparison of the lower limit of normal to the fixed ratio method for the diagnosis of airflow obstruction at high altitudes: a large cross-sectional survey of subjects living between 3000-4700 m above sea level.

BACKGROUND: There is no general agreement on the preferential use of a fixed ratio (FR) of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7 vs. the lower limit of normal (LLN) of FEV1/FVC to define airflow obstruction. Determining the impact of these different cut-off levels in people living at high altitudes has not been studied. We assessed the prevalence of airflow obstruction and its clinical characteristics in residents living at high altitude using a fixed ratio and the LLN of FEV1/FVC according to Global Lung Initiative 2012 (GLI) reference values. METHODS: Using a multistage stratified sampling method, 3702 participants (aged ≥ 15 years) living at an altitude of 3000-4700 m in Tibet were included. RESULTS: 11.4% and 7.7% of participants had airflow obstruction according to GLI-LLN and a fixed FEV1/FVC cut-off value, respectively. The participants in the FR-/LLN+ group were younger, predominantly female, more frequently exposed to household air pollution, and had a higher proportion of chronic obstructive pulmonary disease assessment test scores ≥ 10 than those in the FR-/LLN- group. They also had a significantly lower FEV1 and a higher frequency of small airway dysfunction. Compared with the participants of the FR+/LLN+ group, those in the FR-/LLN+ group showed no significant difference in the risk factors for airflow obstruction and respiratory symptoms, but had a lower prevalence of small airway dysfunction. CONCLUSIONS: Defining airflow obstruction according to LLN, instead of using an FR, identified younger individuals with more frequent clinical symptoms of airflow obstruction and small airway dysfunction.

Home Use of Mechanical Insufflation/Exsufflation in Adult Patients in Western Switzerland.

BACKGROUND: Mechanical insufflation/exsufflation (MI-E) devices are often prescribed to patients with inefficient cough and recurrent infections, but their use in the home setting is not well characterized. OBJECTIVE: The objective of this study was to report a real-life experience and identify factors that are associated with home MI-E use in adult patients. METHODS: This is a cross-sectional observational study of adult subjects with neurological disease using MI-E at home for more than 3 months. RESULTS: A total of 43 patients were included. Median age (interquartile range) was 48 (31-64) years. The most common diagnosis was muscular dystrophy (n = 15), followed by multiple sclerosis (n = 7) and amyotrophic lateral sclerosis (n = 7). 24 subjects (56%) reported using the MI-E at least once weekly. Based on device data downloads, the median objective use was 23% of days analysed (approximately 2 times per week). The vast majority (94%) of all participants reported using the device at least daily during an infectious episode, while 62% reported having used the device in emergency situations such as bronchoaspiration. Reported use correlated well with objective use (r = 0.82). Most subjects reported an improvement in their respiratory health (64%) and were satisfied with the device (78%). Higher reported and objective use were associated with increased symptoms (p = 0.001) and higher satisfaction with the device (p = 0.008). We found no association between frequency of use and baseline cough peak flow (CPF), bulbar impairment, non-invasive ventilation use, living environment, or supervised administration. CONCLUSION: Regular home MI-E use was associated with greater symptom burden and overall satisfaction with the device and was not influenced by baseline CPF. Patients without substantial bronchorrhea might not use the MI-E regularly but might still need to use the device at home during acute events. Therefore, familiarity with the MI-E via appropriate and repeated practical training is crucial.

Cost-effectiveness of outpatient versus inpatient non-invasive ventilation setup in obesity hypoventilation syndrome: the OPIP trial.

BACKGROUND: Current guidelines recommend that patients with obesity hypoventilation syndrome (OHS) are electively admitted for inpatient initiation of home non-invasive ventilation (NIV). We hypothesised that outpatient NIV setup would be more cost-effective. METHODS: Patients with stable OHS referred to six participating European centres for home NIV setup were recruited to an open-labelled clinical trial. Patients were randomised via web-based system using stratification to inpatient setup, with standard fixed level NIV and titrated during an attended overnight respiratory study or outpatient setup using an autotitrating NIV device and a set protocol, including home oximetry. The primary outcome was cost-effectiveness at 3 months with daytime carbon dioxide (PaCO2) as a non-inferiority safety outcome; non-inferiority margin 0.5 kPa. Data were analysed on an intention-to-treat basis. Health-related quality of life (HRQL) was measured using EQ-5D-5L (5 level EQ-5D tool) and costs were converted using purchasing power parities to £(GBP). RESULTS: Between May 2015 and March 2018, 82 patients were randomised. Age 59±14 years, body mass index 47±10 kg/m2 and PaCO2 6.8±0.6 kPa. Safety analysis demonstrated no difference in ∆PaCO2 (difference -0.27 kPa, 95% CI -0.70 to 0.17 kPa). Efficacy analysis showed similar total per-patient costs (inpatient £2962±£580, outpatient £3169±£525; difference £188.20, 95% CI -£61.61 to £438.01) and similar improvement in HRQL (EQ-5D-5L difference -0.006, 95% CI -0.05 to 0.04). There were no differences in secondary outcomes. DISCUSSION: There was no difference in medium-term cost-effectiveness, with similar clinical effectiveness, between outpatient and inpatient NIV setup. The home NIV setup strategy can be led by local resource demand and patient and clinician preference. TRIAL REGISTRATION NUMBERS: NCT02342899 and ISRCTN51420481.

Airflow obstruction and small airway dysfunction following pulmonary tuberculosis: a cross-sectional survey.

OBJECTIVES: Pulmonary function impairment and chronic respiratory symptoms after tuberculosis are relatively common in low-income and middle-income countries. We aimed to estimate the impact of post-tuberculosis (post-TB) on pulmonary function. METHODS: This large cross-sectional, population-based study included subjects aged 15 years or older with technically acceptable postbronchodilator spirometry measurements. Post-TB was diagnosed on the basis of radiological evidence and/or medical history. Airflow obstruction was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal of Global Lung Function Initiative (GLI) lung function equations. Small airway dysfunction was diagnosed if at least two of the following indicators were less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50% or FEF 75%. RESULTS: In this population sample (N=8680, mean age: 40.1 years), 610 (7.0% (95% CI 6.5 to 7.6) participants were post-TB. Post-TB subjects had more frequent respiratory symptoms (46.8% vs 28.3%). Among post-TB subjects, 130 (21.3% (95% CI 18.1 to 24.8)) had airflow obstruction; OR of airflow obstruction was significantly associated with post-TB after adjustment for other confounding factors (OR 1.31, 95% CI 1.05 to 1.62). Post-TB was also associated with small airway dysfunction (OR 1.28, 95% CI1.07 to 1.53), which was present in 297 (48.9% (95% CI 33.9 to 53.0)) post-TB subjects. CONCLUSIONS: Our findings support existing knowledge that post-TB is positively associated with pulmonary function impairment and make for frequent respiratory symptoms. Post-TB should be considered as a potentially important cause of airflow obstruction and respiratory symptoms in patients originating from countries with a high burden of tuberculosis.

Effect of Respiratory Events on Health-Related Quality of Life in Patients Treated with Long-Term Noninvasive Ventilation.

BACKGROUND: Long-term noninvasive ventilation (NIV) can increase or maintain health-related quality of life (HRQoL) for patients with chronic hypercapnic respiratory failure (CHRF). Evidence from studies systematically assessing how NIV-specific factors influence HRQoL is limited. OBJECTIVES: The objective of this study was to describe HRQoL measured by the Severe Respiratory Insufficiency Questionnaire (SRI) in patients with CHRF treated with long-term NIV and to analyze the associations between HRQoL and hypoxemia, hypercapnia, and respiratory events such as apneas, hypopneas (AHI), and patient ventilator asynchrony (PVA) occurring during long-term NIV. METHODS: We included sixty-seven stable patients with established long-term NIV due to neuromuscular disease or thoracic cage disorders in a prospective cross-sectional study at Oslo University Hospital. Patients answered the SRI and underwent daytime arterial blood gases, nocturnal pulse oximetry, sleep polygraphy, and nocturnal transcutaneous CO2. RESULTS: The mean global SRI for 62 patients was 64.8 ± 14.5, with the highest score in SRI Social Relationships (79.5 ± 15.6). There were no differences in HRQoL between the different patient groups. Compliant patients had a significantly higher score in SRI Attendant and Sleep. Residual nocturnal hypoxemia affected both the subscale SRI "Respiratory Complaints" and SRI "Attendant Symptoms and Sleep." Persisting daytime hypercapnia, nocturnal hypoventilation, and high AHI affected the subscale SRI "Anxiety" negatively, while frequent PVA was associated with a lower score in SRI "Physical Function." CONCLUSION: In a group of patients with long-term NIV, undesired respiratory events during NIV are associated with lower HRQoL in several of the SRI subscales. We suggest designing interventional studies to confirm the possible relationship between HRQoL and respiratory events during long-term NIV.

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

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

Monitoring Long Term Noninvasive Ventilation: Benefits, Caveats and Perspectives.

Long term noninvasive ventilation (LTNIV) is a recognized treatment for chronic hypercapnic respiratory failure (CHRF). COPD, obesity-hypoventilation syndrome, neuromuscular disorders, various restrictive disorders, and patients with sleep-disordered breathing are the major groups concerned. The purpose of this narrative review is to summarize current knowledge in the field of monitoring during home ventilation. LTNIV improves symptoms related to CHRF, diurnal and nocturnal blood gases, survival, and health-related quality of life. Initially, patients with LTNIV were most often followed through elective short in-hospital stays to ensure patient comfort, correction of daytime blood gases and nocturnal oxygenation, and control of nocturnal respiratory events. Because of the widespread use of LTNIV, elective in-hospital monitoring has become logistically problematic, time consuming, and costly. LTNIV devices presently have a built-in software which records compliance, leaks, tidal volume, minute ventilation, cycles triggered and cycled by the patient and provides detailed pressure and flow curves. Although the engineering behind this information is remarkable, the quality and reliability of certain signals may vary. Interpretation of the curves provided requires a certain level of training. Coupling ventilator software with nocturnal pulse oximetry or transcutaneous capnography performed at the patient's home can however provide important information and allow adjustments of ventilator settings thus potentially avoiding hospital admissions. Strategies have been described to combine different tools for optimal detection of an inefficient ventilation. Recent devices also allow adapting certain parameters at a distance (pressure support, expiratory positive airway pressure, back-up respiratory rate), thus allowing progressive changes in these settings for increased patient comfort and tolerance, and reducing the requirement for in-hospital titration. Because we live in a connected world, analyzing large groups of patients through treatment of "big data" will probably improve our knowledge of clinical pathways of our patients, and factors associated with treatment success or failure, adherence and efficacy. This approach provides a useful add-on to randomized controlled studies and allows generating hypotheses for better management of HMV.

Nontuberculous Mycobacteria under Scrutiny in the Geneva Area (2015-2020).

BACKGROUND: Nontuberculous mycobacteria (NTM) are increasingly identified in industrialized countries, and their role as pathogens is more frequently recognized. The relative prevalence of NTM strains shows an important geographical variability. Thus, establishing the local relative prevalence of NTM strains is relevant and useful for clinicians. METHODS: Retrospective analysis (2015-2020) of a comprehensive database was conducted including all results of cultures for mycobacteria in a University Hospital (Geneva, Switzerland), covering a population of approximately 500,000 inhabitants. All NTM culture-positive patients were included in the analyses. Patients' characteristics, NTM strains, and time to culture positivity were reported. RESULTS: Among 38,065 samples analyzed during the study period, 411 were culture-positive for NTM, representing 236 strains, and 231 episodes of care which occurred in 222 patients. Patients in whom NTM were identified were predominantly female (55%), with a median age of 62 years, and a low BMI (median: 22.6 kg/m2). The Mycobacterium avium complex (MAC) was the most frequently identified group (37% of strains) followed by Mycobacterium gordonae (25%) and Mycobacterium xenopi (12%) among the slowly growing mycobacteria (SGM), while the Mycobacterium chelonae/abscessus group (11%) were the most frequently identified rapidly growing mycobacteria (RGM). Only 19% of all patients were treated, mostly for pulmonary infections: the MAC was the most frequently treated NTM (n = 19, 43% of cases in patients treated) followed by RGM (n = 15, 34%) and M. xenopi (n = 6, 14%). Among those treated, 23% were immunosuppressed, 12% had pulmonary comorbidities, and 5% systemic comorbidities. Cultures became positive after a median of 41 days (IQR: 23; 68) for SGM and 28 days (14; 35) for RGM. CONCLUSIONS: In Western Switzerland, M. avium and M. gordonae were the most prevalent NTM identified. Positive cultures for NTM led to a specific treatment in 19% of subjects. Patients with a positive culture for NTM were mostly female, with a median age of 62 years, a low BMI, and a low prevalence of immunosuppression or associated severe comorbidities.

Time to Detection of Growth for Mycobacterium tuberculosis in a Low Incidence Area.

Background: Diagnosis of Mycobacterium tuberculosis (MTB) infection can be confirmed by Xpert assays within hours. However, when sample size does not allow performing both culture and Xpert, or if Xpert is negative, then formal diagnosis of MTB relies on culture and time to detection of growth (TDG) becomes critical for clinical management. Objectives: To determine TDG in Xpert negative samples, or in samples in which Xpert could not be performed, in a low-incidence area for MTB. Methods: Retrospective analysis (2015-2020) of a database including all cultures for mycobacteria in a University Hospital covering approximately 500'000 inhabitants. Analysis was restricted to culture positive (C+) samples for MTB for which 1/Xpert was negative or could not be performed because of limited sample volume, and 2/collected from subjects treated less than 24 hours. TDG was analyzed according to microscopy, origin of sample (pulmonary or not) and presence of cavitation. Results: Among 837 C+ samples for MTB, 236 samples (80% of respiratory origin) from 147 patients fulfilled study criteria; 78 samples (49 patients, 33%) were acid-fast bacilli (AFB) positive. Median (IQR) TDG was 25 (17; 40) days for all samples. TDG exceeded 28 days in 43% of samples and was significantly shorter in AFB+ vs AFB- samples, and samples from cavitary vs non cavitary or extra-thoracic disease. Conclusions: In Xpert negative samples, or samples for which Xpert could not be performed, TDG exceeded 4 weeks in 43% of samples. AFB+ and samples from cavitary lung disease had a significantly shorter TDG.

Oral function in amyotrophic lateral sclerosis patients: A matched case-control study.

BACKGROUND & AIMS: Patients with amyotrophic lateral sclerosis (ALS) develop swallowing difficulties with the progression of the disease. The present study aimed at comparing oral function and body composition between ALS patients and healthy controls, and at evaluating which parameters are the most discriminant between both groups. METHODS: We included ALS patients at the start of their multidisciplinary follow-up at the Geneva University Hospitals and healthy age-, gender-, and dental status-matched adults. We assessed the severity of the disease through the ALS Functional Rating Scale and the swallowing difficulties through the EAT-10 score. We performed an intraoral examination of the dental status, and measured chewing performance, bite, lip and tongue force, saliva weight, and body composition. Group comparisons were performed with t-tests or Mann-Whitney tests as appropriate. Linear discriminant analysis was used to determine the most discriminant parameters between groups. RESULTS: Twenty-six ALS patients (bulbar onset: n = 7, median (IQR) ALS Functional Rating Scale: 37 (11)) were included. The ALS patients had a significantly lower chewing performance (p < 0.001), lip force (p < 0.001), tongue force (p = 0.002), saliva weight (p < 0.004) and fat-free mass index (p < 0.001) as compared to the healthy individuals, and a higher EAT-10 score (p < 0.001). In ALS patients, a low chewing performance was correlated with a low bite (r = -0.45, p < 0.05)) and tongue force (r = -0.59, p < 0.05). The most discriminant parameters between both groups, by order of importance, were chewing performance, fat-free mass index and saliva weight and allowed the calculation of a discriminant function. CONCLUSION: Compared to healthy controls, ALS patients have significant alterations of oral function and body composition. The most discriminant parameters between both groups were chewing performance, fat-free mass index and saliva volume. It remains to be demonstrated whether oral parameters predict outcome. CLINICAL TRIAL REGISTRY: clinicaltrials.gov, identifier: NCT01772888.

Breathlessness and COVID-19: A Call for Research.

Breathlessness, also known as dyspnoea, is a debilitating and frequent symptom. Several reports have highlighted the lack of dyspnoea in a subgroup of patients suffering from COVID-19, sometimes referred to as "silent" or "happy hyp-oxaemia." Reports have also mentioned the absence of a clear relationship between the clinical severity of the disease and levels of breathlessness reported by patients. The cerebral complications of COVID-19 have been largely demonstrated with a high prevalence of an acute encephalopathy that could possibly affect the processing of afferent signals or top-down modulation of breathlessness signals. In this review, we aim to highlight the mechanisms involved in breathlessness and summarize the pathophysiology of COVID-19 and its known effects on the brain-lung interaction. We then offer hypotheses for the alteration of breathlessness perception in COVID-19 patients and suggest ways of further researching this phenomenon.

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

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.

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

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.

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

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.