Relationship Between Cognitive-Behavioral Impairment and Clinical and Functional Parameters in ALS and Reliability of the Edinburgh Cognitive and Behavioural ALS Screen to Assess ALS: Preliminary Findings.

BACKGROUND: Although it is widely recognized that a high percentage of individuals with amyotrophic lateral sclerosis (ALS) have cognitive and behavioral impairment, the associated clinical and functional parameters remain unknown. ALS is typically assessed via screening tests, such as the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). OBJECTIVE: To investigate the relationship between cognitive-behavioral impairment and other clinical and functional parameters and to compare the assessment results from a set of standardized neuropsychological tests with those from the ECAS. METHODS: Forty individuals with ALS participated in the study. We assessed attention, memory and learning ability, and executive function using a set of standardized neuropsychological tests and the ECAS. Sociodemographic variables, time since onset of symptoms, time since diagnosis, and functional respiratory values were recorded. RESULTS: No relationship was found between time since onset of symptoms and time since definitive diagnosis and either attention (P=0.206, 0.314, respectively), memory and learning ability (P=0.618, 0.692), or executive function (P=0.844, 0.583). The set of standardized neuropsychological tests identified an impairment in executive function in 29% of the participants, whereas the ECAS identified it in 89%. CONCLUSIONS: We found no relationship between cognitive-behavioral impairment and time since onset of symptoms nor time since ALS diagnosis. Because the ECAS does not correctly reflect the executive function of individuals with ALS, function-specific neuropsychological tests are preferred. Test selection must take into account individuals' physical characteristics and their consequent ability to respond gesturally or orally.

Performance of a Highly Sensitive Mycobacterium tuberculosis Complex Real-Time PCR Assay for Diagnosis of Pulmonary Tuberculosis in a Low-Prevalence Setting: a Prospective Intervention Study.

The potential impact of routine real-time PCR testing of respiratory specimens from patients with presumptive tuberculosis in terms of diagnostic accuracy and time to tuberculosis treatment inception in low-prevalence settings remains largely unexplored. We conducted a prospective intervention cohort study. Respiratory specimens from 1,020 patients were examined by acid-fast bacillus smear microscopy, tested by a real-time Mycobacterium tuberculosis complex PCR assay (Abbott RealTime MTB PCR), and cultured in mycobacterial media. Seventeen patients tested positive by PCR (5 were acid-fast bacillus smear positive and 12 acid-fast bacillus smear negative), and Mycobacterium tuberculosis was recovered from cultures for 12 of them. Patients testing positive by PCR and negative by culture (n = 5) were treated and deemed to have responded to antituberculosis therapy. There were no PCR-negative/culture-positive cases, and none of the patients testing positive for nontuberculous mycobacteria (n = 20) yielded a positive PCR result. The data indicated that routine testing of respiratory specimens from patients with presumptive tuberculosis by the RealTime MTB PCR assay improves the tuberculosis diagnostic yield and may reduce the time to antituberculosis treatment initiation. On the basis of our data, we propose a novel mycobacterial laboratory algorithm for tuberculosis diagnosis.

Critical role of fractalkine (CX3CL1) in cigarette smoke-induced mononuclear cell adhesion to the arterial endothelium.

BACKGROUND: Cigarette smoking is an important risk factor for the development of cardiovascular disease, yet the pathways through which this may operate are poorly understood. Therefore, the mechanism underlying cigarette smoke (CS)-induced arterial endothelial dysfunction and the potential link with fractalkine/CX(3)CL1 upregulation were investigated. METHODS AND RESULTS: Stimulation of human arterial umbilical endothelial cells (HUAECs) with pathophysiological concentrations of CS extract (1% CSE) increased CX(3)CL1 expression. Neutralisation of CX(3)CL1 activity under dynamic flow conditions significantly inhibited CSE-induced mononuclear cell adhesion to HUAECs (67%). The use of small interfering RNA (siRNA) revealed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (Nox5) but not Nox2 or Nox4 is the main NADPH isoform involved in CSE-induced CX(3)CL1 upregulation and mononuclear cell arrest. Knock down of HUAEC tumour necrosis factor α expression with siRNA or pharmacological inhibition of p38 mitogen-activated protein kinase and nuclear factor κB also abolished these responses. Interestingly, circulating monocytes and lymphocytes from patients with chronic obstructive pulmonary disease (COPD) (n=29) versus age-matched controls (n=23) showed CX(3)CR1overexpression. Furthermore, CX(3)CL1 neutralisation dramatically diminished their enhanced adhesiveness to CSE-stimulated HUAECs. Finally, when animals were exposed for 3 days to CS, a mild inflammatory response in the lung was observed which was accompanied by enhanced CX(3)CL1 expression in the cremasteric arterioles, an organ distant from the lung. CS exposure resulted in increased leukocyte-arteriolar endothelial cell adhesion which was significantly reduced (51%) in animals lacking CX(3)CL1 receptor (CX(3)CR1). CONCLUSIONS: These results suggest that CS induces functional CX(3)CL1 expression in arterial endothelium and leukocytes from patients with COPD show increased CX(3)CL1-dependent adhesiveness. Therefore, targeting the CX(3)CL1/CX(3)CR1 axis might prevent COPD-associated cardiovascular disorders.

Paving the Way for Climate Neutral and Resilient Historic Districts.

Climate change is a major global threat to our society's urban areas, with the majority of Europe's population living in cities and their cultural heritage. Historic districts of significant cultural value and the communities connected to these places have an important role to play in fostering location-based identity and economy, social cohesion, innovation, urban regeneration, and climate change adaptation. Thus, it is important to make historic districts climate resilient, by jointly considering climate change adaptation, disaster risk management, heritage management, and sustainable urban development. However, this is often a major challenge for local and regional administrators and relevant stakeholders. This paper constitutes the first major result of the EU R&I Task Force for Climate Neutral and Resilient Historic Urban Districts. It provides an overview of the challenges faced by practitioners and researchers when jointly addressing the needs of resilient historic districts and provides an initial set of recommendations produced by the task force to address these challenges. These challenges cover different issues around five topics (i) data availability, use and its management, (ii) the common responsibility fragmentation in policy and governance, (iii) the challenge on integrating local knowledge and traditions in resilience building, (iv) the difficulties around the co-ownership and co-production in governance and (v) the importance of mainstreaming heritage management in adaptation and resilience policies.

Home tracheotomy mechanical ventilation in patients with amyotrophic lateral sclerosis: causes, complications and 1-year survival.

BACKGROUND: Home tracheotomy mechanical ventilation (HTMV) can prolong survival in patients with amyotrophic lateral sclerosis (ALS) when non-invasive ventilation (NIV) fails, but knowledge about HTMV is scarce. The aim of this study was to determine the causes of tracheotomy and the main issues of 1-year HTMV in a cohort of patients with ALS. METHODS: A prospective study of all patients needing HTMV was performed in a referral respiratory care unit (RCU) from April 2001 to January 2010. Patients' informed decisions about HTMV were fully respected. Caregivers were trained and could telephone the RCU. Hospital staff made home visits. RESULTS: All patients (n=116) agreed to participate and a tracheotomy was needed for 76, mainly due to bulbar dysfunction. Of the 38 who had a tracheotomy, in 21 it was performed in an acute setting and in 17 as a non-emergency procedure. In 19 patients the tracheotomy was related to the inadequacy of mechanically assisted coughing (MAC) to maintain normal oxygen saturation. During HTMV, 19 patients required hospitalisation, 12 with respiratory problems. The 1-year survival rate was 78.9%, with a mean survival of 10.39 months (95% CI 9.36 to 11.43). Sudden death was the main cause of death (n=9) and only one patient died from respiratory causes. No predictive factors for survival were found. CONCLUSIONS: Besides NIV inadequacy, the ineffectiveness of mechanically assisted coughing appears to be a relevant cause of tracheotomy for patients with ALS with severe bulbar dysfunction. Patients choosing HTMV provided by a referral RCU could have a good 1-year survival rate, respiratory problems being the main cause of hospitalisation but not of death.

Mechanical Insufflation-Exsufflation With Oscillations in Amyotrophic Lateral Sclerosis With Home Ventilation via Tracheostomy.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) applied via tracheostomy tubes in patients with amyotrophic lateral sclerosis (ALS) who are on home mechanical ventilation via tracheostomy is an effective procedure for respiratory secretion management. Nonetheless, tenacious secretions may remain and increase the risk of respiratory infections. The aim of this study was to determine whether adding oscillations to MI-E could reduce the rate of respiratory infections and the need for bronchoscopy to remove secretions in patients with ALS on home mechanical ventilation via tracheostomy. METHODS: This was a 2-y, prospective, crossover study. Subjects were treated with conventional MI-E and MI-E with oscillations for 2 alternate 6-month periods. Data were collected on episodes of respiratory infections, hospital admission, and number of bronchoscopy procedures. RESULTS: In the 19 ALS subjects enrolled, the median (interquartile range [IQR]) number of acute respiratory infections per subject was 1.0 (0.5-2.0) in the MI-E period and 0.0 (0.0-2.0) in the MI-E plus oscillations period (P = .92). The median (IQR) number of hospital stays was 0.0 (0.0-1.0) in the MI-E period and 0.0 (0.0-1.0) in the MI-E plus oscillations period (P = .80). The median (IQR) number of bronchoscopies per subject was 0.0 (0.0-1.0) in MI-E period and 0.0 (0.0-0.5) in the MI-E plus oscillations period (P = .26). MI-E plus oscillations treatment had no impact on the risk of respiratory infections (odds ratio 3.71, 95% CI 0.81-16.84, P = .09) or the need for bronchoscopy (odds ratio 2.70, 95% CI 0.44-16.68, P = .29). CONCLUSIONS: Adding oscillations to MI-E therapy in subjects with ALS on home mechanical ventilation via tracheostomy did not decrease the risk of respiratory infections, hospital admission, or need for bronchoscopy.

Effect of one-year dextromethorphan/quinidine treatment on management of respiratory impairment in amyotrophic lateral sclerosis.

Treatment with Dextromethorphan/Quinidine (DM/Q) has demonstrated benefit on pseudobulbar affect and bulbar function in amyotrophic lateral sclerosis (ALS). The aim of this study was to assess whether DM/Q could provide long-term improvement in bulbar function and thereby prolong noninvasive respiratory management in ALS. MATERIALS AND METHODS: This prospective, case-cohort study, recruited ALS patients with bulbar dysfunction. Subjects included were compared with cross-matched historical controls. Cases received DM/Q (20/10 mg twice daily) during one-year follow-up; bulbar dysfunction was evaluated with the Norris scale bulbar subscore (NBS) and bulbar subscale of AlSFRS-R (ALSFRSb). RESULTS: In total, 21 cases and 20 controls were enrolled, of whom noninvasive respiratory muscle assistance failed in 6 (28.5%) patients in the DM/Q group, compared with 4 patients (20.0%) in the control group (p = 0.645). Time from study onset to failure of respiratory muscle aids was 5.50 + 1.31 months in the DM/Q group and 5.20 + 1.15 months in the control group (p = 0.663). The adjusted OR for the effect of treatment on failure of noninvasive respiratory muscle aids was 2.12 (95%CI 0.23-33.79, p = 0.592). In the DM/Q group an impairment in scores was found in NBS (F = 19.26, p = 0.000) and ALSFRS-Rb (F = 12.71, p = 0.001) across different months of the study. CONCLUSION: Treatment with DM/Q in ALS is unable to prolong noninvasive respiratory management, and moreover, has no effect on long-term deterioration of bulbar function. Notwithstanding the results on bulbar function, DM/Q was found to improve pseudobulbar affect during one-year follow-up.

Usefulness of Oscillations Added to Mechanical In-Exsufflation in Amyotrophic Lateral Sclerosis.

BACKGROUND: Assisted coughing via mechanical in-exsufflation (MI-E) is a first-line treatment for secretion management in patients with amyotrophic lateral sclerosis (ALS) with unassisted CPF < 4.25 L/s. Some devices enable oscillations to be added to MI-E (MI-E+O). We sought to determine whether adding oscillations to MI-E enables a reduction in the use of invasive secretion management procedures (ie, bronchoscopy or tracheostomy) in subjects with ALS. METHODS: We conducted a 12-month, prospective, randomized follow-up study of subjects with ALS for whom assisted coughing techniques were indicated. One group was treated with oscillations in addition to MI-E (MI-E+O), and the other group was treated with conventional MI-E. RESULTS: 29 subjects were included in the MI-E group and 27 subjects were included in the MI-E+O group. Five subjects (8.9%) required invasive techniques for secretion management (3 in the MI-E group and 2 in the MI-E+O group, P = .70). Treatment with MI-E+O did not alter the risk of invasive procedures (odds ratio 0.69, 95% CI 0.10-4.50, P = .70). The mean number of respiratory infections was 0.58 ± 0.16 in the MI-E group and 0.025 ± 0.08 in the MI-E+O group (P = .10). Survival was 8.96 ± 0.18 months in the MI-E group and 7.70 ± 0.70 months in the MI-E+O group (P = .10). CONCLUSION: Adding oscillations to MI-E did not enable a reduction in the need to perform invasive procedures for secretion management in subjects with ALS.

Unstable control of breathing can lead to ineffective noninvasive ventilation in amyotrophic lateral sclerosis.

Upper airway obstruction with decreased central drive (ODCD) is one of the causes of ineffective noninvasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS). The aim of this study is to determine the mechanism responsible for ODCD in ALS patients using NIV. This is a prospective study that included ALS patients with home NIV. Severity of bulbar dysfunction was assessed with the Norris scale bulbar subscore; data on upper or lower bulbar motor neuron predominant dysfunction on physical examination were collected. Polysomnography was performed on every patient while using NIV and the ODCD index (ODCDI: number of ODCD events/total sleep time) was calculated. To determine the possible central origin of ODCD, controller gain was measured by inducing a hypocapnic hyperventilation apnoea. Sonography of the upper airway during NIV was performed to determine the location of the ODCD. 30 patients were enrolled; three (10%) had ODCDI >5 h-1. The vast majority of ODCD events were produced during non-rapid eye movement sleep stages and were a consequence of an adduction of the vocal folds. Patients with ODCDI >5 h-1 had upper motor neuron predominant dysfunction at the bulbar level, and had greater controller gain (1.97±0.33 versus 0.91±0.36 L·min-1·mmHg-1; p<0.001) and lower carbon dioxide (CO2) reserve (4.00±0.00 versus 10.37±5.13 mmHg; p=0.043). ODCDI was correlated with the severity of bulbar dysfunction (r= -0.37; p=0.044), controller gain (r=0.59; p=0.001) and CO2 reserve (r= -0.35; p=0.037). ODCD events in ALS patients using NIV have a central origin, and are associated with instability in the control of breathing and an upper motor neuron predominant dysfunction at the bulbar level.

Importance of noninvasively measured respiratory muscle overload among the causes of hospital readmission of COPD patients.

AIM: To evaluate the influence of respiratory muscle overload and right cardiac overload among the possible risk factors of hospital readmission in a 1-year follow-up of a cohort of patients with moderate-to-severe COPD. METHODS: A total of 112 COPD patients who were admitted consecutively to the hospital for acute exacerbation. At hospital discharge, we evaluated the conventional clinical and functional determinations in addition to the pressure-time index (PTI), which is obtained using the equation PTI = (Pawo/Pimax) x (Ti/Ttot) x 100, where Pawo represents the mean airway pressure measured at the mouth during spontaneous breathing, Pimax is the maximal inspiratory pressure, Ti is the inspiratory time, and Ttot is the total breathing cycle time. A cardiac echo-Doppler examination was carried out when patients were in stable condition and presented clinical signs of right cardiac overload prior to inclusion in the study. RESULTS: Multivariate analysis showed that the use of long-term oxygen therapy (LTOT) and high PTI (> 0.25) were independently related to the risk of hospital readmission. Patients receiving LTOT had higher Paco(2) (p < 0.05), FEV(1) percent predicted (p < 0.05), FVC percent predicted (p < 0.05), and Pao(2) (p < 0.05), and had higher Paco(2) (p < 0.05). An elevated systolic pulmonary arterial pressure (> 40 mm Hg) was also independently related, but only 28 patients had echo-Doppler data that could be used. CONCLUSIONS: At hospital discharge, noninvasively measured respiratory muscle overload as well as the use of LTOT were associated with an increased risk of hospital readmission for exacerbation in patients with moderate-to-severe COPD.

Bulbar impairment score and survival of stable amyotrophic lateral sclerosis patients after noninvasive ventilation initiation.

There is general agreement that noninvasive ventilation (NIV) prolongs survival in amyotrophic lateral sclerosis (ALS) and that the main cause of NIV failure is the severity of bulbar dysfunction. However, there is no evidence that bulbar impairment is a contraindication for NIV. The aim of this study was to determine the effect of bulbar impairment on survival in ALS patients with NIV. ALS patients for whom NIV was indicated were included. Those patients who refused NIV were taken as the control group. 120 patients who underwent NIV and 20 who refused NIV were included. The NIV group presented longer survival (median 18.50 months, 95% CI 12.62-24.38 months) than the no-NIV group (3.00 months, 95% CI 0.82-5.18 months) (p<0.001) and also in those patients with severe bulbar dysfunction (13.00 months (95% CI 9.49-16.50 months) versus 3.00 months (95% CI 0.85-5.15 months), p<0.001). Prognostic factors for ALS using NIV, adjusted for NIV failure, were severity of bulbar dysfunction (hazard ratio (HR) 0.5, 95% CI 0.92-0.97; p=0.001) and time spent with oxygen saturation measured by pulse oximetry <90% (%sleepSpO2 <90) using NIV (HR 1.12, 95% CI 1.01-1.24; p=0.02). Severe bulbar impairment in ALS does not always prevent NIV from being used, but the severity of bulbar dysfunction at NIV initiation and %sleepSpO2 <90 while using NIV appear to be the main prognostic factors of NIV failure in ALS.

Effectiveness of assisted and unassisted cough capacity in amyotrophic lateral sclerosis patients.

Decreased cough capacity during a respiratory infection is one of the main causes of acute respiratory failure and hospitalisation in amyotrophic lateral sclerosis (ALS). OBJECTIVE: To determine whether a respiratory measurement could identify the effectiveness of cough capacity in ALS during a respiratory infection. METHODS: This was a prospective study of all ALS patients who were treated at a respiratory care unit due to a respiratory infection from 2012 to 2016. The effectiveness of unassisted and assisted coughing was evaluated and respiratory function tests were performed during the acute episode. RESULTS: Forty-eight ALS patients were enrolled, with only four having an effective unassisted cough. The variable which predicted unassisted cough effectiveness was peak cough flow (PCF) (OR 4499.27; 95%CI 3.60-3219086.19; p = 0.022) with a cut-off point of 2.77 L/s (166 L/min). For manually assisted coughing, the predictor of cough effectiveness was manually assisted PCF (cut-off point of 2.82-169 L/min) (OR 2198.602; 95% CI 3.750-1351691.42; p = 0.019). Mechanically assisted PCF (cut-off point of 2.95-177 L/min) was found to be the predictor of mechanically assisted coughing effectiveness (OR 23.40; 95% CI 2.11-258.96; p = 0.010). CONCLUSIONS: During a respiratory infection in ALS patients, the effectiveness of assisted and unassisted cough capacity depends on the PCF generated.

Cigarette Smoke Increases Endothelial CXCL16-Leukocyte CXCR6 Adhesion In Vitro and In Vivo. Potential Consequences in Chronic Obstructive Pulmonary Disease.

Cardiovascular disease (CVD) is a major comorbidity in chronic obstructive pulmonary disease (COPD). Although the mechanism of its development remains largely unknown, it appears to be associated with cigarette consumption and reduced lung function. Therefore, the aim of this study was to investigate the potential link between water-soluble cigarette smoke extract (CSE)-induced endothelial dysfunction and the function of CXCL16/CXCR6 axis on the initial attachment of leukocytes, in addition to its possible impact on COPD-associated systemic inflammation. To do this, we employed several experimental approaches, including RNA silencing and flow cytometry analysis, the dynamic flow chamber technique, and intravital microscopy in the cremasteric arterioles of animals exposed to cigarette smoke (CS). CSE-induced arterial CXCL16 expression, leading to increased platelet-leukocyte and mononuclear cell adhesiveness. CSE-induced CXCL16 expression was dependent on Nox5 expression and subsequent RhoA/p38 MAPK/NF-κB activation. Flow cytometry analysis revealed that COPD patients (n = 35) presented greater numbers of activated circulating platelets (PAC-1+ and P-selectin+) expressing CXCL16 and CXCR6 as compared with age-matched controls (n = 17), with a higher number of CXCR6+-platelets in the smoking COPD group than in ex-smokers. This correlated with enhanced circulating CXCR6+-platelet-leukocyte aggregates in COPD patients. The increase in circulating numbers of CXCR6-expressing platelets and mononuclear cells resulted in enhanced platelet-leukocyte and leukocyte adhesiveness to CSE-stimulated arterial endothelium, which was greater than that found in age-matched controls and was partly dependent on endothelial CXCL16 upregulation. Furthermore, CS exposure provoked CXCL16-dependent leukocyte-arteriolar adhesion in cremasteric arterioles, which was significantly reduced in animals with a nonfunctional CXCR6 receptor. In conclusion, we provide the first evidence that increased numbers of CXCR6-expressing circulating platelets and mononuclear leukocytes from patients with COPD might be a marker of systemic inflammation with potential consequences in CVD development. Accordingly, CXCL16/CXCR6 axis blockade might constitute a new therapeutic approach for decreasing the risk of CVD in COPD patients.

Effect of High-Frequency Oscillations on Cough Peak Flows Generated by Mechanical In-Exsufflation in Medically Stable Subjects With Amyotrophic Lateral Sclerosis.

BACKGROUND: Mechanically assisted coughing with mechanical in-exsufflation (MI-E) is recommended for noninvasive management of respiratory secretions in amyotrophic lateral sclerosis (ALS). To improve the effectiveness of the technique, a new device combining MI-E with high-frequency oscillations (HFO) has been developed. This work aimed to assess the effect of HFO on the cough peak flow generated by MI-E in medically stable subjects with ALS. METHODS: This was a prospective study that included subjects with ALS in a medically stable condition. Cough peak flow generated by MI-E was measured in 4 situations: without HFO, with HFO during insufflation, with HFO during exsufflation, and with HFO in both cycles. The parameters used were: insufflation pressure of +40 cm H2O, exsufflation pressure of -40 cm H2O, insufflation time 2 s, exsufflation time 3 s, amplitude of oscillations 10 cm H2O, and frequency of oscillations 15 Hz. RESULTS: Forty-seven subjects with ALS were included: 66% males, 68.2 ± 9.2 y, 40% with bulbar onset, FVC = 1.7 ± 1.1 L, percent-of-predicted FVC = 54.4 ± 26.6%, cough peak flow = 3.8 ± 2.2 L/s, PImax = -39.4 ± 26.4 cm H2O, revised ALS scale = 28.5 ± 9.3, Norris bulbar subscore = 26.1 ± 10.4. No statistical differences were found in cough peak flow generated by MI-E in the 4 situations (without HFO = 4.0 ± 1.2 L/s, with insufflation HFO = 3.9 ± 1.2 L/s, with exsufflation HFO = 4.1 ± 1.2 L/s, with in-exsufflation HFO = 3.9 ± 1.1 L/s). CONCLUSIONS: The addition of HFO to mechanically assisted coughing with MI-E does not have an effect on the cough peak flow of medically stable subjects with ALS.

Effect of a short-term psychological intervention on the anxiety and depression of amyotrophic lateral sclerosis patients.

This study evaluated the effectiveness of a psychological intervention in amyotrophic lateral sclerosis patients, consisting of four semi-structured sessions of cognitive behavioural therapy combined with counselling techniques. An intervention group and a control group were established. The Hospital Anxiety and Depression Scale was used to assess levels of anxiety and depression. In total, fifty-four patients took part. Prior to the intervention, the intervention group displayed rates of 63.3 and 36.7 per cent for anxiety and depression, respectively, falling to 16.7 and 10.0 per cent afterwards. The psychological intervention demonstrated potential for the reduction of levels of anxiety and depression in amyotrophic lateral sclerosis patients.

Noninvasive ventilation during the weaning process in chronically critically ill patients.

Chronically critically ill patients often undergo prolonged mechanical ventilation. The role of noninvasive ventilation (NIV) during weaning of these patients remains unclear. The aim of this study was to determine the value of NIV and whether a parameter can predict the need for NIV in chronically critically ill patients during the weaning process. We conducted a prospective study that included chronically critically ill patients admitted to Spanish respiratory care units. The weaning method used consisted of progressive periods of spontaneous breathing trials. Patients were transferred to NIV when it proved impossible to increase the duration of spontaneous breathing trials beyond 18 h. 231 chronically critically ill patients were included in the study. 198 (85.71%) patients achieved weaning success (mean weaning time 25.45±16.71 days), of whom 40 (21.4%) needed NIV during the weaning process. The variable which predicted the need for NIV was arterial carbon dioxide tension at respiratory care unit admission (OR 1.08 (95% CI 1.01-1.15), p=0.013), with a cut-off point of 45.5 mmHg (sensitivity 0.76, specificity 0.67, positive predictive value 0.76, negative predictive value 0.97). NIV is a useful tool during weaning in chronically critically ill patients. Hypercapnia despite mechanical ventilation at respiratory care unit admission is the main predictor of the need for NIV during weaning.

Bulbar impairment score predicts noninvasive volume-cycled ventilation failure during an acute lower respiratory tract infection in ALS.

UNLABELLED: Amyotrophic lateral sclerosis (ALS) patients can suffer episodes of lower respiratory tract infections (LRTI) leading to an acute respiratory failure (ARF) requiring noninvasive ventilation (NIV). AIM: To determine whether clinical or functional parameters can predict noninvasive management failure during LRTI causing ARF in ALS. MATERIAL AND METHOD: A prospective study involving all ALS patients with ARF requiring NIV in a Respiratory Care Unit. NIV was provided with volume-cycled ventilators. RESULTS: 63 ALS patients were included (APACHE II: 14.93±3.56, Norris bulbar subscore (NBS): 18.78±9.68, ALSFRS-R: 19.90±6.98, %FVC: 40.01±18.07%, MIC: 1.62±0.74L, PCF 2.51±1.15L/s, PImax -34.90±19.44cmH2O, PEmax 51.20±28.84cmH2O). In 73.0% of patients NIV was successful in averting death or endotracheal intubation. Differences were found between the success and failure in the NBS (22.08±6.15 vs 8.66±3.39, p<0.001), ALSFRS (22.08±6.11 vs 12.71±4.39, p<0.001), PCFMI-E (3.85±0.77 vs 2.81±0.91L/s, p=0.007) and ALS onset (spinal/bulbar 33/13 vs 7/10, p=0.03). The predictor of NIV failure was the NBS (OR 0.53, 95% CI 0.31-0.92, p 0.002) with a cut-off point of 12 (S 0.93; E 0.97; PPV 0.76; NPV 0.97). CONCLUSIONS: NBS can predict noninvasive management failure during LRTI in ALS.

Predictors of need for noninvasive ventilation during respiratory tract infections in medically stable, non-ventilated subjects with amyotrophic lateral sclerosis.

BACKGROUND: Acute lower respiratory infections can impair muscle strength in patients with amyotrophic lateral sclerosis (ALS). When associated with an increase in load on the respiratory system, this situation may precipitate hypercapnic respiratory failure in non-ventilated patients with ALS. The aim of this study was to determine whether a clinical or functional parameter can predict the need for noninvasive ventilation (NIV) during an acute respiratory infection for medically stable, non-ventilated patients with ALS. METHODS: This was a prospective study involving all non-ventilated subjects with ALS admitted due to an acute respiratory infection to a respiratory care unit from a tertiary hospital. RESULTS: Thirty-two non-ventilated subjects with ALS were admitted to our respiratory care unit due to an acute respiratory infection: 60.72 ± 10.54 y, 13 males, 23 with spinal onset, FVC of 1.58 ± 0.83 L, FVC of 56.21 ± 23.15% of predicted, peak cough flow of 3.41 ± 1.77 L/s, maximum insufflation capacity of 1.87 ± 0.94 L, revised Amyotrophic Lateral Sclerosis Functional Rating Scale score of 22.80 ± 8.83, and Norris bulbar score of 23.48 ± 12.14. Fifteen subjects required NIV during the episode. Logistic regression analysis showed that the only predictors of need for NIV were percent-of-predicted FVC (odds ratio of 1.06, 95% CI 1.01-1.11, P = .02) and peak cough flow (odds ratio of 2.57, 95% CI 1.18-5.59, P = .02). CONCLUSIONS: In medically stable, non-ventilated patients with ALS, measurement of percent-of-predicted FVC and peak cough flow can predict the need for NIV during an acute lower respiratory tract infection.

Tolerance of Volume Control Noninvasive Ventilation in Subjects With Amyotrophic Lateral Sclerosis.

BACKGROUND: Noninvasive ventilation (NIV) tolerance has been identified as an independent predictor of survival in amyotrophic lateral sclerosis (ALS). Volume control continuous mandatory ventilation (VC-CMV) NIV has been associated with poor tolerance. The aim of this study was to determine the tolerance of subjects with ALS to VC-CMV NIV. METHODS: This was a prospective study involving subjects with ALS who were treated with VC-CMV NIV. Respiratory and functional parameters were recorded when the subjects began ventilatory support. NIV tolerance was evaluated after 3 months. RESULTS: Eighty-seven subjects with ALS were included. After 3 months, 80 subjects (92%) remained tolerant of NIV. Tolerant subjects presented greater survival (median 22.0 months, 95% CI 14.78-29.21) than intolerant subjects (median 6.0 months, 95% CI 0.86-11.13) (P = .03). The variables that best predicted NIV tolerance were mechanically assisted cough peak flow (P = .01) and percentage of time spent with SpO2 < 90% at night while on NIV (P = .03) CONCLUSIONS: VC-CMV NIV provides high rates of NIV tolerance in subjects with ALS. Mechanically assisted cough peak flow and percentage of time spent with SpO2 < 90% at night while using NIV are the 2 factors associated with tolerance of VC-CMV NIV in subjects with ALS.

Efficacy of mechanical insufflation-exsufflation in medically stable patients with amyotrophic lateral sclerosis.

OBJECTIVE: To determine under what circumstances the use of mechanical insufflation-exsufflation (MI-E) can generate clinically effective expiratory flows for airway clearance (> 2.7 L/s) for clinically stable patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHOD: Twenty-six consecutive patients with ALS were studied, 15 with severe bulbar dysfunction. Using a pneumotachograph and with the aid of an oronasal mask, we measured FVC, FEV(1), peak cough flow (PCF), maximum insufflation capacity (MIC), PCF generated from a maximum insufflation MIC (PCFMIC), and PCF generated by MI-E (PCFMI-E). MI-E was delivered at +/- 40 cm H(2)O. Maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) at the mouth were also measured. RESULTS: Although both groups had a similar time from ALS symptom onset to diagnosis, statistical differences (p < 0.05) were found between nonbulbar and bulbar patients in lung function and cough capacity parameters: FVC, 2.58 +/- 1.24 L vs 1.62 +/- 0.74 L; FEV(1), 2.26 +/- 1.18 L vs 1.54 +/- 0.69 L; PImax, - 93.45 +/- 47.47 cm H(2)O vs - 3.64 +/- 25.07 cm H(2)O; PEmax, 140.45 +/- 75.98 cm H(2)O vs 69.93 +/- 32.14 cm H(2)O; MIC, 3.02 +/- 1.22 L vs 1.97 +/- 0.75 L; PCF, 5.91 +/- 2.55 L/s vs 3.42 +/- 1.44 L/s; PCFMIC, 6.68 +/- 2.71 L/s vs 4.00 +/- 1.48 L/s; and PCFMI-E, 4.34 +/- 0.82 L/s vs 3.35 +/- 0.77 L/s. Four patients with bulbar dysfunction and MIC > 1 L had PCFMI-E < 2.7 L/s. The receiver operating characteristic (ROC) curve analysis showed PCFMIC of 4 L/s predicting those patients with PCFMIC greater than PCFMI-E. CONCLUSION: MI-E is able to generate clinically effective PCFMI-E (> 2.7 L/s) for stable patients with ALS, except for those with bulbar dysfunction who also have a MIC > 1 L and PCFMIC <2.7 L/s who probably have severe dynamic collapse of the upper airways during the exsufflation cycle. Clinically stable patients with mild respiratory dysfunction and PCFMIC > 4 L/s might not benefit from MI-E except during an acute respiratory illness.