Impact of diabetes mellitus on the respiratory function of amyotrophic lateral sclerosis patients.

BACKGROUND AND PURPOSE: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). The impact of diabetes mellitus (DM) on respiratory function of ALS patients is uncertain. METHODS: A retrospective cohort study was carried out. From the 1710 patients with motor neuron disease followed in our unit, ALS and progressive muscular atrophy patients were included. We recorded demographic characteristics, functional ALS rating scale (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and its subscores at first visit, respiratory function tests, arterial blood gases, phrenic nerve amplitude (PhrenAmpl), and mean nocturnal oxygen saturation (SpO2 mean). We excluded patients with other relevant diseases. Two subgroups were analysed: DIAB (patients with DM) and noDIAB (patients without DM). Independent t-test, χ2 , or Fisher exact test was applied. Binomial logistic regression analyses assessed DM effects. Kaplan-Meier analysis assessed survival. p < 0.05 was considered significant. RESULTS: We included 1639 patients (922 men, mean onset age = 62.5 ± 12.6 years, mean disease duration = 18.1 ± 22.0 months). Mean survival was 43.3 ± 40.7 months. More men had DM (p = 0.021). Disease duration was similar between groups (p = 0.063). Time to noninvasive ventilation (NIV) was shorter in DIAB (p = 0.004); total survival was similar. No differences were seen for ALSFRS-R or its decay rate. At entry, DIAB patients were older (p < 0.001), with lower forced vital capacity (p = 0.001), arterial oxygen pressure (p = 0.01), PhrenAmpl (p < 0.001), and SpO2 mean (p = 0.014). CONCLUSIONS: ALS patients with DM had increased risk of respiratory impairment and should be closely monitored. Early NIV allowed for similar survival rate between groups.

Respiratory phenotypes in amyotrophic lateral sclerosis as determined by respiratory questions on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised and their relation to respiratory tests.

BACKGROUND AND PURPOSE: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear. METHODS: Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO2 mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors. RESULTS: We included 276 patients (153 men, onset age = 62.6 ± 11.0 years, disease duration = 13.0 ± 9.6 months, spinal onset in 182) with mean survival of 40.1 ± 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1 > G2 > G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO2 mean. Independent predictors for G2 were MIP and SpO2 mean; for G3, the only independent predictor was PhrenAmpl. CONCLUSIONS: These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3.

Respiratory function tests in amyotrophic lateral sclerosis: The role of maximal voluntary ventilation.

BACKGROUND: Pulmonary function tests are routinely used to measure progression in ALS. This study aimed to assess the change of various respiratory tests, in particular maximal voluntary ventilation (MVV), which evaluates respiratory endurance. METHODS: A group of 51 patients were assessed 3 times (T1, T2, T3, separated by 5.4 months), including slow (SVC) and forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), maximal inspiratory (MIP) and expiratory (MEP) pressures, MVV, and sniff nasal inspiratory pressure (SNIP). In addition, body mass index (BMI), ALSFRS-R and phrenic nerve responses were obtained 4 times. Patients with dementia and marked bulbar involvement were excluded. RESULTS: Mean ALSFRS-R was high at entry (42.9) and its decline was moderately slow at 0.4/month. FVC and FEV1 declined significantly in the three time frames analysed. MVV reduced significantly only between T1-T3 and SVC between T2-T3, and MIP, MEP, PEF and SNIP did not change significantly. The amplitude and the latency of the motor response of the phrenic nerve changed significantly, and BMI declined significantly in most time periods, and ALSFRS-R changed significantly in the 4 time periods. We found a strong correlation between MVV, and FVC, SVC, FEV1, SNIP, phrenic nerve amplitude/area (p < 0.001), and markedly with PEF (rho = 0.821) and ALSFRS-R (rho = 0.713). CONCLUSIONS: Our study of early affected patients supports the use of a set of volitional and non-volitional respiratory tests to assess disease progression, rather than any single test. We found MVV a potentially useful marker of pulmonary function in ALS.

Rapid Evaluation of the Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus Tests.

The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n = 125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, 10 influenza A, 10 influenza B and 20 respiratory syncytial virus specimens. Results were compared to in-country standard-of-care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive percentage agreement (PPA) = 95.2%, negative percentage agreement (NPA) = 95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA = 100%, NPA = 98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus, respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard-of-care tests.

Assessing chemoreflexes and oxygenation in the context of acute hypoxia: Implications for field studies.

Carotid chemoreceptors detect changes in PO2 and elicit a peripheral respiratory chemoreflex (PCR). The PCR can be tested through a transient hypoxic ventilatory response test (TT-HVR), which may not be safe nor feasible at altitude. We characterized a transient hyperoxic ventilatory withdrawal test in the setting of steady-state normobaric hypoxia (13.5-14% FIO2) and compared it to a TT-HVR and a steady-state poikilocapnic hypoxia test, within-individuals. No PCR test magnitude was correlated with any other test, nor was any test magnitude correlated with oxygenation while in steady-state hypoxia. Due to the heterogeneity between the different PCR test procedures and magnitudes, and the confounding effects of alterations in CO2 acting on both central and peripheral chemoreceptors, we developed a novel method to assess prevailing steady-state chemoreflex drive in the context of hypoxia. Quantifying peak hypoxic/hyperoxic responses at low altitude may have minimal utility in predicting oxygenation during ascent to altitude, and here we advance a novel index of chemoreflex drive.

Phrenic nerve stimulation is more sensitive than ultrasound measurement of diaphragm thickness in assessing early ALS progression.

AIMS OF THE STUDY: To compare the assessment of respiratory decline with conventional tests, measurement of diaphragm compound muscle action potential (CMAP) to phrenic nerve stimulation and diaphragm thickness to ultrasound (US) investigation in amyotrophic lateral sclerosis (ALS) patients followed for a short period of time. PATIENTS AND METHODS: We evaluated in 40 consecutive ALS patients, the clinical functional scale (ALSFRS-R), forced vital capacity (FVC), maximal voluntary ventilation (MVV), maximal inspiratory (MIP) and expiratory (MEP) pressures, sniff nasal inspiratory pressure (SNIP), Diaphragm-CMAP (latency and amplitude) and diaphragm US (maximal and minimal diaphragm thickness during full inspiration and expiration, respectively). Patients were evaluated at study entry and 4 months later. RESULTS: Clinical functional assessment (ALSFRS-R), MEP, SNIP, and Diaphragm-CMAP amplitude declined significantly. Conversely, FVC, MVV, MIP, and diaphragm thickness showed a non-significant decline. We found significant correlations between all variables measured at both evaluation times. CONCLUSION: In this study, we included patients who might be potentially eligible for a clinical trial and re-evaluated them within 4 months. In this short time, diaphragm thickness as assessed by US is not sensitive to detect changes. However, Diaphragm-CMAP amplitude was confirmed to be a sensitive non-volitional method to measure respiratory function in ALS.

Ultrasound for assessment of diaphragm in ALS.

OBJECTIVE: To evaluate the correlation between diaphragm thickness assessed by ultrasound (US) with respiratory function tests and the diaphragm motor responses, in patients with amyotrophic lateral sclerosis (ALS). METHODS: 42 consecutive ALS patients were studied (11 with bulbar-onset), excluding patients with marked orofacial paresis. Investigation included: revised ALS functional rating scale (ALSFRS-R), forced vital capacity (FVC), maximal voluntary ventilation (MVV), maximal inspiratory (MIP) and expiratory (MEP) pressures, nasal inspiratory pressure during sniff (SNIP); peak-to-peak amplitude of the diaphragmatic motor response to phrenic nerve stimulation (Diaphragm-CMAP), diaphragmatic thickness measured by ultrasound during maximal inspiration and during maximal expiration. Patients were analysed in bulbar or spinal subgroups. Correlations and multiple linear regression models were studied. RESULTS: The mean age at disease onset was 58.4 ± 11.1 years and with a mean disease duration of 17.8 ± 13.6 months. Ultrasound studies of diaphragm thickness in full inspiration correlated with diaphragm CMAP in the whole population and in spinal-onset patients; and were similar in the two groups. Multiple linear modelling showed that FVC, SNIP and MVV were dependent on the change of thickness (p=0.001, 0.001 and 0.020, respectively) and that MIP and MEP were related to diaphragm CMAP p=0.003 and p=0.025, respectively). CONCLUSION: Diaphragm thickness correlates with Diaphragm-CMAP, except in bulbar-onset patients. Respiratory tests are dependent on both diaphragm thickness and Diaphragm-CMAP. SIGNIFICANCE: US thickness of the diaphragm correlates with the number of functional motor units as assessed by the phrenic nerve motor amplitude.

Influência das variações da postura sentada na função respiratória: revisão de literatura / Influence of sitting posture variations in respiratory function: review of the literature

INTRODUÇÃO: Os efeitos da postura sobre a função respiratória têm motivado pesquisas com o objetivo de rastrear alterações nos mecanismos de adaptação à mudança da postura corporal. A importância desse conhecimento está em compreender como essas alterações podem interferir na função respiratória de indivíduos saudáveis e em condições especiais, como obesos e gestantes. OBJETIVO: Realizar uma revisão bibliográfica para descrever o conhecimento produzido sobre as alterações da função respiratória em diferentes posturas corporais, em especial na postura sentada. MÉTODOS: Foram definidos os conceitos-chave da pesquisa: postura, postura sentada, testes respiratórios e função respiratória ou pulmonar; em seguida determinou-se o período de pesquisa que envolveu os anos de 2000 a 2010 (inclusive) e as bases de dados pesquisadas: SciELO, PEDro, Cochrane e Pubmed. RESULTADO: Encontrou-se que as primeiras pesquisas sobre função respiratória enfocavam alterações encontradas em mudanças significativas da postura corporal, geralmente em indivíduos saudáveis. O aprimoramento científico permitiu a incorporação tecnológica aos métodos de avaliação da função respiratória. Nos estudos sobre postura sentada, observa-se que as alterações são significativas em indivíduos com doenças pulmonares, cardíacas e idosos, entre outros, e que, mesmo em indivíduos saudáveis, as alterações nos testes de função podem ultrapassar a variação dos valores considerados normais para uma dada posição. CONCLUSÃO: São necessários maiores estudos para determinar o momento em que essas alterações podem ser significativas em indivíduos saudáveis e quais as alternativas possíveis para minimizar esses efeitos.

INTRODUCTION: The effects of posture on respiratory function has motivated research in order to detect changes in the adaptation mechanisms related to changes in body posture. The importance of this knowledge is to understand how these changes may affect respiratory function in healthy subjects and in special conditions such as obesity and pregnancy. OBJECTIVE: To conduct a literature review to describe the knowledge produced about the changes in lung function in different body positions, specially in the sitting posture. METHODS: The selected keywords were: posture, sitting or seated posture, respiratory tests and lung or respiratory function, then we defined that the research period was 10 years, from 2000 to 2010 (inclusive) and the databases searched were: SciELO, PEDro, Cochrane and Pubmed. RESULTS: We found that early research focused on respiratory function changes found in significant changes in body posture, often in healthy individuals. The scientific improvement allowed to incorporate technological methods of assessment of respiratory function. In studies of sitting posture is observed that the changes are significant in individuals with chronic lung, heart and elderly, among others, and that even in healthy subjects the changes in the function tests can exceed the range of values considered normal for a given position. CONCLUSION: It takes more study to determine the point at which these changes can be significant in healthy subjects and what the possible alternatives to minimize these effects.

Amyotrophic lateral sclerosis: combined nutritional, respiratory and functional assessment / Esclerose lateral amiotrófica: correlações dos indicadores da avaliação nutricional, funcional e respiratória

OBJECTIVE: To establish correlations between nutritional, functional and respiratory indices of patients with amyotrophic lateral sclerosis (ALS). METHOD: Twenty patients (13 appendicular - GA and 7 bulbar - GB) were included in the multidisciplinary study at the Neurological Clinic Ambulatory of the University of Campinas Hospital. RESULTS: Among the GA type significant correlation was observed between maximal inspiratory (MIP) and expiratory (MEP) pressure (r= -0.76), MEP and pulse oxymetry (r=0.58), MIP and percent weight loss ( percentWL; r=0.59), and between MIP, total and subscale respiratory scores (ALSFRS-R) with percentWL. With regard to the GB, correlation was found between MEP and body mass index (BMI) (r=0.97). In both GA and GB correlations were noticed between the BMI and the variables mass (kg), fat ( percent), arm and wrist circumference (cm), and tricipital, subscapular and supra-iliac skinfolds (mm), as well as the arm muscle circumference (cm) and fatty arm muscular area (mm²). CONCLUSION: It is suggested that the application of simple anthropometric measurements could be useful in routine monitoring of patients with ALS.

OBJETIVO: Correlacionar os indicadores utilizados na avaliação nutricional, funcional e respiratória de indivíduos com esclerose lateral amiotrófica (ELA). MÉTODO: Vinte pacientes (13 apendiculares - GA e 7 bulbares - GB) foram incluídos no estudo usando parâmetros nutricionais, respiratórios e escala funcional (ALSFRS-R). RESULTADOS: Entre os pacientes do GA, as correlações observadas foram: pressão inspiratória máxima (PImax) e expiratória máxima (PEmax) (r= -0,76); PEmax e oximetria de pulso (r=0,58); PImax e porcentagem de perda de peso ( por centoPP) (r=0,59); e entre PImax, escore ALSFRS-R com por centoPP. No GB, houve correlação entre MEP e índice de massa corporal (IMC) (r=0,97). Em GA e GB, observaram-se correlação entre IMC e as variáveis: massa, gordura ( por cento), circunferência braquial e punho, pregas cutâneas tricipital, subescapular e supra-ilíaca, circunferência muscular do braço (cm), área muscular gordurosa do braço (mm²). CONCLUSÃO: Sugere-se a aplicação deste conjunto de medidas durante a evolução clínica de indivíduos com ELA.