Dr Shakeeb Moosavi
BSc, PhD, FHEA
Reader in Clinical Physiology
School of Biological and Medical Sciences
Role
After graduating in Physiology from King’s College London, I worked as research technician in child health at Leicester Royal Infirmary. In 1988 I became a clinical physiologist at Charing Cross Hospital and began a PhD studying exercise breathing. My first postdoctoral position (also at Charing Cross) involved neurophysiological research on severely brain-injured patients.
In 1998 I moved to Harvard to research mechanisms of breathlessness and returned in 2004 to a lectureship at Imperial College. In 2010 I spent a year as research scientist with UK Spinal Cord Injury Research Network at Stoke Mandeville Hospital.
I joined Oxford Brookes Universtity in 2011 as a Senior Lecturer and research group lead. I am also a Physiological Society Representative for Oxford Brookes University.
Areas of expertise
- Cardiorespiratory integration
- Respiratory control and sensation
- Dyspnoea (breathlessness) mechanisms, assessment, management
Teaching and supervision
Courses
- Biological Sciences (Human Biosciences) (BSc (Hons), MBiol)
- Biomedical Science (BSc (Hons))
- Medical Science (BSc (Hons))
Modules taught
- Scientific Skills (Level 4-single)-Tutor
- Professional and Experimental Skills (Level 4-single)-Tutor
- Human Structure and Function (Level 4-double)-Lectures
- Research Methods (Level 5-single)-Project coursework supervisor
- Integrated Physiology (Level 5-double) Lectures, practicals, PBL
- Pathophysiology (Level 6-double) Module Leader
- Neuroscience (Level 6-double) Module Leader
- Research Projects (Level 6-double) Supervisor
I fulfil the following roles:
- Academic Adviser (UG Levels 4-6)
- Research projects supervisor (UG Levels 5-6)
- Module Leader (UG levels 5-6)
- Director of Studies (Postgraduate)
Supervision
- Jan'21 -Dec'23 (Director of studies; Self-funded PhD)
Dr. Maria Yermolitska "Inhaled hydroxygas for dyspnoea relief" -(Active) - Sep'20 - Aug'23 (Director of studies; Groome Studentship)
Mr.Tom Chapman "Respiratory control and dysfunction in Parkinson's Disease" -(Active) - Sep’16 – Aug’19 (Director of Studies; Groome Studentship)
Ms. Charlotte Golding “Effects of neurosurgical intervention and neurological damage on dyspnoea“ - (Awarded August 2020)
(currently studying Medicine) - Jan’15 – Jan’21 (Director of Studies; part-time direct PhD)
Dr. Joanna Grogono “Mechanism of dyspnoea in heart failure” -(Awarded February 2021)
Now appointed as a Consultant in Cardiology - Oct’12 – Sep’16 (Director of Studies; Groome Studentship)
Dr. Emmanuel Debrah “Cerebral mechanisms of dyspnoea and its relief” -(Awarded March 2017)
Currently employed as a clinical trials coordinator in Neuroscience
Research
My primary research interest is to find out how breathlessness (‘dyspnoea’) arises so that more effective drugs can be developed to relieve dyspnoea when the underlying disease can’t be cured. The multidisciplinary research involves experiments on healthy volunteers and various patients who are inordinately breathless.
I have tested hypotheses regarding ‘air hunger’ (an unpleasant component of dyspnoea), validated ways to induce specific components of dyspnoea using specially-constructed breathing circuits and developed a unique questionnaire that quantifies overall breathlessness (intensity and unpleasantness) and is based on the language patients use to describe their experience. The work has guided on-going clinical studies including randomised-controlled trials to test novel interventions.
I have a three-pronged research strategy:
- To study patients undergoing neurological interventions or suffering neurological damage in order to better understand neurophysiological mechanisms of breathlessness.
- To use the improved understanding of neurophysiological mechanisms of breathlessness to identify and trial new pharmacological interventions for intractable breathlessness.
- To address emerging concerns in clinical physiology, particularly those that have the potential to stretch the NHS to breaking point.
Research impact
Mechanisms and management of breathlessness is at the core of the research strategy outlined below. There is an urgent clinical need for effective and safe interventions for breathlessness relief when underlying pathophysiology is incurable. This need has been amplified by the coronavirus pandemic.
Centres and institutes
Groups
Publications
Journal articles
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Chapman TP, Farrell SM, Plaha P, Green AL, Moosavi SH, 'Blunted perception of breathlessness in three cases of low grade insular-glioma'
Frontiers in Neuroscience 18 (2024)
ISSN: 1662-4548 eISSN: 1662-453XAbstractPublished here Open Access on RADARBetter understanding of breathlessness perception addresses an unmet clinical need for more effective treatments for intractable dyspnoea, a prevalent symptom of multiple medical conditions. The insular-cortex is predominantly activated in brain-imaging studies of dyspnoea, but its precise role remains unclear. We measured experimentally-induced hypercapnic air-hunger in three insular-glioma patients before and after surgical resection. Tests involved one-minute increments in inspired CO2, raising end-tidal PCO2 to 7.5 mmHg above baseline (38.5 ± 5.7 mmHg), whilst ventilation was constrained (10.7 ± 2.3 L/min). Patients rated air-hunger on a visual analogue scale (VAS). Patients had lower stimulus–response (2.8 ± 2 vs. 11 ± 4 %VAS/mmHg; p = 0.004), but similar threshold (40.5 ± 3.9 vs. 43.2 ± 5.1 mmHg), compared to healthy individuals. Volunteered comments implicated diminished affective valence. After surgical resection; sensitivity increased in one patient, decreased in another, and other was unable to tolerate the ventilatory limit before any increase in inspired CO2.We suggest that functional insular-cortex is essential to register breathlessness unpleasantness and could be targeted with neuromodulation in chronically-breathless patients. Neurological patients with insula involvement should be monitored for blunted breathlessness to inform clinical management
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Rhys GH, Wakeling T, Moosavi SH, Moore JP, Dawes H, Knight M, Inada-Kim M, Christensen EF, Subbe CP
, 'Feasibility and accuracy of the 40-steps desaturation test to determine outcomes in a cohort of patients presenting to hospital with and without COVID-19'
Clinical Medicine 22 (3) (2022) pp.203-209
ISSN: 1470-2118 eISSN: 1473-4893AbstractPublished here Open Access on RADARDesaturation on exercise has been suggested as a predictive feature for deterioration in COVID-19. The objective of this paper was to determine the feasibility and validity for the 40-steps desaturation test.A prospective observational cohort study was undertaken in patients assessed in hospital prior to discharge. One-hundred and fifty-two participants were screened between November 2020 and February 2021, and 64 were recruited to perform a 40-steps desaturation test. Patients who were able to perform the test were younger and less frail. Four patients were readmitted to hospital and one patient deteriorated within 30 days but no patient died.The majority of patients showed little change in saturations during the test, even with pre-existing respiratory pathology. Change in saturations, respiratory rate, heart rate and breathlessness were not predictive of death or readmission to hospital within 30 days. Of 13 patients who had a desaturation of 3% or more during exercise, none was readmitted to hospital within 30 days.Not enough patients with COVID-19 could be recruited to the study to provide evidence for the safety of the test in this patient group.The 40-steps desaturation test requires further evaluation to assess clinical utility.
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Holton P, Huang Y, Bahuri NFA, Boccard S, Hyam JA, Paterson DJ, Dorrington KL, Aziz TZ, Moosavi SH, Green AL, 'Differential responses to breath‐holding, voluntary deep breathing and hypercapnia in left and right dorsal anterior cingulate'
Experimental Physiology 106 (3) (2021) pp.726-735
ISSN: 0958-0670 eISSN: 1469-445XAbstractPublished hereThe role of subcortical structures and cerebral cortex in the maintenance of respiratory homeostasis in humans remains poorly understood. Emerging evidence suggests an important role of the anterior cingulate cortex (ACC) in respiratory control. In this study, local field potentials (LFPs) from dorsal ACC were recorded in humans through implanted deep brain electrodes during several breathing activities, including voluntary activities of breath-holding and deep breathing, and involuntary activities of inspiration of varying concentrations of carbon dioxide (1%, 3%, 5% and 7%). We found that the breath-holding task induced significant unilateral left-sided ACC changes in LFP power, including an increased activity in lower frequency bands (3-5 Hz) and decreased activity in higher frequency bands (12-26 Hz). The respiratory task involving reflex increase in ventilation due to hypercapnia (raised inspired CO2 ) was associated with bilateral changes in activity of the ACC (again with increased activity in lower frequency bands and reduced activity in higher frequency bands). The voluntary breathing task with associated hypocapnia (deep breathing) induced bilateral changes in activity within low frequency bands. Furthermore, probabilistic diffusion tractography analysis showed left-sided connection of the ACC with the insula and frontal operculum, and bilateral connections within subsections of the cingulate gyrus and the thalamus. This electrophysiological analysis provides direct evidence for a role of the ACC in respiratory control in humans.
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Bendell C, Moosavi SH, Herigstad M, 'Low-level carbon monoxide exposure affects BOLD fMRI signal'
Journal of Cerebral Blood Flow & Metabolism 40 (11) (2019) pp.2215-2224
ISSN: 0271-678X eISSN: 1559-7016AbstractPublished here Open Access on RADARBlood Oxygen Level Dependent (BOLD) fMRI is a common technique for measuring brain activation that could be affected by low-level carbon monoxide (CO) exposure from e.g. smoking. This study aimed to probe the vulnerability of BOLD fMRI to CO and determine whether it may constitute a significant neuroimaging confound. Low-level (6ppm exhaled) CO effects on BOLD response were assessed in 12 healthy never-smokers on two separate experimental days (CO and air control). fMRI tasks were breath-holds (hypercapnia), visual stimulation and fingertapping. BOLD fMRI response was lower during breath holds, visual stimulation and fingertapping in the CO protocol compared to the air control protocol. Behavioural and physiological measures remained unchanged. We conclude that BOLD fMRI might be vulnerable to changes in baseline CO, and suggest exercising caution when imaging populations exposed to elevated CO levels. Further work is required to fully elucidate the impact on CO on fMRI and its underlying mechanisms.
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Hyam JA, Wang S, Roy H, Moosavi SH, Martin S, Brittain JS, Coyne T, Silburn P, Aziz TZ, Green AL, 'The pedunculopontine region and breathing in Parkinson’s disease'
Annals of Clinical and Translational Neurology 6 (5) (2019) pp.837-847
ISSN: 2328-9503 eISSN: 2328-9503AbstractPublished here Open Access on RADARObjective. Respiratory abnormalities such as upper airway obstruction are common in Parkinson's disease (PD) and are an important cause of mortality and morbidity. We tested the effect of pedunculopontine region (PPNr) stimulation on respiratory maneuvers in human participants with PD, and separately recorded PPNr neural activity reflected in the local field potential (LFP) during these maneuvers. Methods. Nine patients with deep brain stimulation electrodes in PPNr, and seven in globus pallidus interna (GPi) were studied during trials of maximal inspiration followed by forced expiration with stimulation OFF and ON. Local field potentials (LFPs) were recorded in the unstimulated condition. Results. PEFR increased from 6.41 ± 0.63 L/sec in the OFF stimulation state to 7.5 L ± 0.65 L/sec in the ON stimulation state (z = −2.666, df = 8, P = 0.024). Percentage improvement in PEFR was strongly correlated with proximity of the stimulated electrode contact to the mesencephalic locomotor region in the rostral PPN (r = 0.814, n = 9, P = 0.008). Mean PPNr LFP power increased within the alpha band (7–11 Hz) during forced respiratory maneuvers (1.63 ± 0.16 μV2/Hz) compared to resting breathing (0.77 ± 0.16 μV2/Hz; z = −2.197, df = 6, P = 0.028). No changes in alpha activity or spirometric indices were seen with GPi recording or stimulation. Percentage improvement in PEFR was strongly positively correlated with increase in alpha power (r = 0.653, n = 14 (7 PPNr patients recorded bilaterally), P = 0.0096). Interpretation. PPNr stimulation in PD improves indices of upper airway function. Increased alpha‐band activity is seen within the PPNr during forced respiratory maneuvers. Our findings suggest a link between the PPNr and respiratory performance in PD.
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Green AL, Debrah E, Roy H, Rebelo P, Moosavi SH, 'Thalamic deep brain stimulation may relieve breathlessness in COPD'
Brain Stimulation 12 (3) (2019) pp.827-828
ISSN: 1935-861X eISSN: 1876-4754AbstractPublished here Open Access on RADARThe cerebral mechanisms of dyspnoea (breathlessness) are not well understood. Neuroimaging studies of experimentally induced dyspnoea in healthy individuals have identified several cortical areas that might form a neural network for perception of dyspnoea [1], much like those identified for pain perception [2]. However, functional imaging studies alone do not reveal neurophysiological pathways and may miss putative targets for dyspnoea relief. The objective of this study was to assess the effects of Deep Brain Stimulation (DBS) of four different brain nuclei on the sensation of dyspnoea in an individual with Chronic Obstructive Pulmonary Disease (COPD) using an established multidimensional dyspnoea tool [3].
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Grogono JC, Butler C, Izadi H, Moosavi SH, 'Inhaled furosemide for relief of air hunger versus sense of breathing effort: a randomized controlled trial'
Respiratory Research 19 (2018)
ISSN: 1465-9921 eISSN: 1465-993XAbstractPublished here Open Access on RADARBackground. Inhaled furosemide offers a potentially novel treatment for dyspnoea, which may reflect modulation of pulmonary stretch receptor feedback to the brain. Specificity of relief is unclear because different neural pathways may account for different components of clinical dyspnoea. Our objective was to evaluate if inhaled furosemide relieves the air hunger component (uncomfortable urge to breathe) but not the sense of breathing work/effort of dyspnoea. Methods. A randomised, double blind, placebo-controlled crossover trial in 16 healthy volunteers studied in a university research laboratory. Each participant received 3 mist inhalations (either 40 mg furosemide or 4 ml saline) separated by 30–60 min on 2 test days. Each participant was randomised to mist order ‘furosemide-saline-furosemide’ (n- = 8) or ‘saline-furosemide-saline’ (n = 8) on both days. One day involved hypercapnic air hunger tests (mean ± SD PCO2 = 50 ± 3.7 mmHg; constrained ventilation = 9 ± 1.5 L/min), the other involved work/effort tests with targeted ventilation (17 ± 3.1 L/min) and external resistive load (20cmH2O/L/s). Primary outcome was ratings of air hunger or work/effort every 15 s on a visual analogue scale. During saline inhalations, 1.5 mg furosemide was infused intravenously to match the expected systemic absorption from the lungs when furosemide is inhaled. Corresponding infusions of saline during furosemide inhalations maintained procedural blinding. Average visual analogue scale ratings (%full scale) during the last minute of air hunger or work/effort stimuli were analysed using Linear Mixed Methods. Results. Data from all 16 participants were analysed. Inhaled furosemide relative to inhaled saline significantly improved visual analogues scale ratings of air hunger (Least Squares Mean ± SE − 9.7 ± 2%; p = 0.0015) but not work/effort (+ 1.6 ± 2%; p = 0.903). There were no significant adverse events. Conclusions. Inhaled furosemide was effective at relieving laboratory induced air hunger but not work/effort in healthy adults; this is consistent with the notion that modulation of pulmonary stretch receptor feedback by inhaled furosemide leads to dyspnoea relief that is specific to air hunger, the most unpleasant quality of dyspnoea.
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Turri-Silva N, Garner DM, Moosavi SH, Ricci-Vitor AL, Christofaro DGD, Junior JN, Vanzella LM, Vanderlei LCM, 'Effects of resistance training protocols on nonlinear analysis of heart rate variability in metabolic syndrome'
Brazilian Journal of Medical and Biological Research 51 (8) (2018)
ISSN: 0100-879X eISSN: 1414-431XAbstractPublished here Open Access on RADARBesides some non-linear measurements used in autonomic modulation (AM) analysis can be suitable using short term series, they usually depend on long time-series of data. To transpose this, chaotic global methods were formulated, putting together heart rate variability (HRV) linear methods. Chaos provides information about vegetative function control related to cardiovascular risks. Applying this method to investigate the complexity of the health condition after resistance training protocols, used as a therapeutic intervention, on AM in metabolic syndrome individuals (MetS) is important. This study aimed to compare the effects of two resistance training programs (conventional vs. functional) in MetS using nonlinear analysis of AM. MetS subjects (n=50), both sexes, aged 40 to 60 years were randomized between two programs. Also, there was a control group (n=12). Both groups performed 30 sessions of training. AM was accessed in chaos domain by chaotic global techniques. The main results showed that both resistance training, functional and conventional, increased chaos when compared to the control group, respectively observed by CFP1 (13.9±17.9 vs. 12.8±14.4 vs. -2.23±7.96; p≤0.05) and CFP3 (15.4±19.8 vs. 21.9±13.2 vs. -4.82±11.4; p≤0.05). In addition, 30 sessions of both resistance programs increase chaos, and nonlinear analysis enables discriminates AM after interventions when compared to control group.
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Banzett RB, Moosavi SH, 'Measuring dyspnoea: new multidimensional instruments to match our 21st century understanding'
European Respiratory Journal 49 (3) (2017)
ISSN: 0903-1936 eISSN: 1399-3003Published here -
Garner DM, Leeuwen P, Grönemeyer D, Moosavi S, 'Assessment of fetal development by HRV and chaotic global techniques'
Journal of Human Growth and Development 26 (2) (2016) pp.162-173
ISSN: 0104-1282AbstractPublished hereIntroduction: Fetal heart rate and its variability during the course of gestation have been extensively re-searched. The overall reduction in heart rate and increase in fetal HRV is associated with fetal growth and the increase in neural integration. The increased complexity of the demands on the cardiovascular system leads to more variation in the temporal course of the heart rate which has been shown to be refl ected in measures of complexity. The aim of this work was to investigate novel complexity measures with respect to their ability to quantify changes over gestational age in individual fetuses consistently and in a stable manner.
Methods: We examined 215 fetal magnetocardiograms (FMCG), each of 5 min duration, in 11 fetuses during the second and third trimesters (at least 10 data sets per fetus). From the FMCG we determined the fetal RR beat durations. For each 5 min time-series of RR intervals we then calculated Shannon entropy, high spectral entropy, high spectral Detrended Fluctuation Analysis, spectral Multi-Taper Method as well as the standard deviation and two commonly used complexity measures: Approximate Entropy and Sample Entropy. For each subject and HRV measure, we performed regression analysis with respect to ges tational age. The coeffi cient of determination R2 was used to es timate ‘goodness-of-fi t’, the slope of the regression indicated the strength of the individual dependency on gestational age.
Results: We found that the new complexity measures do not outperform ApEn.
Conclusion: This study has now rejected the hypothesis that the spectral complexity measures outperform those applied previously
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Binks AP, Evans, KC, Reed JD, Moosavi SH, Banzett RB, 'The time-course of cortico-limbic neural responses to air hunger'
Respiratory Physiology & Neurobiology 204 (2014) pp.78-85
ISSN: 1569-9048Published here -
Boskabady MH, Neamati A, Mohaghegh Hazrati S, Khakzad MR, Moosavi SH, Gholamnezhad Z, 'The preventive effects of natural adjuvants, G2 and G2F on tracheal responsiveness and serum IL-4 and IFN-γ (th1/th2 balance) in sensitized guinea pigs'
Clinics 69 (7) (2014) pp.491-496
ISSN: 1807-5932 eISSN: 1980-5322AbstractPublished hereOBJECTIVE: The effects of natural adjuvants on lung inflammation and tracheal responsiveness were examined in sensitized guinea pigs. METHODS: The responses of guinea pig tracheal chains and the serum levels of interleukin-4 and interferon-gamma were examined in control pigs and three other groups of guinea pigs: the sensitized group and two other sensitized groups treated with either adjuvant G2 or adjuvant G2F (n=7 for each group). Sensitization of the animals was achieved by injection and inhalation of ovalbumin. RESULTS: The results showed that sensitized animals had increased tracheal responsiveness and increased serum levels of interleukin-4 and interferon-gamma compared to controls (p
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Pickering EE, Semple SJ, Nazir MS, Murphy K, Snow TM, Cummin AR, Moosavi SH, Guz A, Holdcroft A, 'Cannabinoid effects on ventilation and breathlessness: A pilot study of efficacy and safety'
Chronic Respiratory Disease 8 (2) (2011) pp.109-118
ISSN: 1479-9723 eISSN: 1479-9731AbstractBased on the neurophysiology of dyspnoea and the distribution of cannabinoid receptors within the central nervous system, we hypothesize that the unpleasantness of breathlessness will be ameliorated in humans by cannabinoids, without respiratory depression. Five normal and four chronic obstructive pulmonary disease (COPD) subjects entered a double blind, randomized, placebo-controlled crossover study with two test days. Subjects received sublingual cannabis extract or placebo. A maximum of 10.8 mg tetrahydrocannabinol and 10 mg cannabidiol were given. Breathlessness was simulated using fixed carbon dioxide loads. Measurements taken were of breathlessness (visual analogue scale [VAS] and breathlessness descriptors), mood and activation, end-tidal carbon dioxide tension and ventilatory parameters. These were measured at baseline and 2 hours post placebo and drug administration. Normal and COPD subjects showed no differences in breathlessness VAS scores and respiratory measurements before and after placebo or drug. After drug administration, COPD subjects picked ‘air hunger’ breathlessness descriptors less frequently compared to placebo. We have shown that breathlessness descriptors may detect an amelioration of the unpleasantness of breathlessness by cannabinoids without a change in conventional breathlessness ratings (VAS). A stimulus more specific for air hunger may be needed to demonstrate directly a drug effect on breathlessness. However, this study shows that the inclusion of respiratory descriptors may contribute to the assessment of drug effects on breathlessness.Published here -
Yorke J, Swigris J, Russell A, Moosavi S, Kwong G, Longshaw M, Jones P, 'Dyspnoea-12 is a valid and reliable measure of breathlessness in patients with ILD'
Chest Journal 139 (1) (2011) pp.159-164
ISSN: 0012-3692AbstractPublished hereObjective: To determine the validity and reliability of the Dyspnoea-12 (D-12) for the assessment of breathlessness in patients with interstitial lung disease (ILD). Methods: 101 patients with ILD completed the D-12 (scaling range 0-36, high score indicates worse dyspnea), MRC dyspnea scale, St George" s Respiratory Questionnaire (SGRQ), and Hospital anxiety and depression scale (HADS) at baseline, and 84 patients completed the D- 12 and a global health transition score at follow-up 2-weeks later. D-12 psychometric properties, including floor and ceiling effects, internal consistency, test-retest reliability and construct validity of the D-12 were examined. Results: The D-12 showed good internal consistency (Cronbach" s a =0.93) and repeatability (Intra-class correlation coefficient = 0.94). Its scores were significantly associated with MRC grade (r = 0.56, p<0.001), SGRQ (symptoms r = 0.57; activities r = 0.78; impacts r = 0.75; total r = 0.79, p<0.001). Confirmatory factor analysis confirmed the previously determined structure of the D-12 in this patient group. Conclusion: In patients with ILD, the patient reported D-12 - a patient reported measure of dyspnoea severity that requires no reference to activity, is a reliable and valid instrument. It is short, simple to complete, and easy to score.
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Gray JEA, Booth S, Brage S, Yorke J, Moosavi S, Bausewein C, Molassiotis A, Johnson M, Farquhar MC, 'Breathlessness Research Interest Group'
Progress in Palliative Care: Science and the Art of Caring 18 (2) (2010) pp.95-98
ISSN: 0969-9260 eISSN: 1743-291XPublished here -
Yorke J, Moosavi S, Shuldham C, Jones P, 'Quantification of dyspnoea using descriptors: development and initial testing of the Dyspnoea-12'
Thorax 65 (1) (2010) pp.21-26
ISSN: 0040-6376 eISSN: 1468-3296AbstractPublished hereRationale: Dyspnoea is a debilitating and distressing symptom that is reflected in different verbal descriptors. Evidence suggests that dyspnoea, like pain perception, consists of sensory quality and affective components. The objective of this study was to develop an instrument that measures overall dyspnoea severity using descriptors that reflect its different aspects. Methods: 81 dyspnoea descriptors were administered to 123 patients with chronic obstructive pulmonary disease (COPD), 129 with interstitial lung disease and 106 with chronic heart failure. These were reduced to 34 items using hierarchical methods. Rasch analysis informed decisions regarding further item removal and fit to the unidimensional model. Principal component analysis (PCA) explored the underlying structure of the final item set. Validity and reliability of the new instrument were further assessed in a separate group of 53 patients with COPD. Results: After removal of items with hierarchical methods (n=47) and items that failed to fit the Rasch model (n=22), 12 were retained. The"-˜Dyspnoea-12" " had good internal reliability (Cronbach" s alpha=0.9) and fit to the Rasch model (x2 p=0.08). Items patterned into two groups called"-˜physical" " (n=7) and"-˜affective" " ( n=5). In the separate validation study, Dyspnoea-12 correlated with the Hospital Anxiety and Depression Scale (anxiety r=0.51; depression r=0.44, p,0.001, respectively), 6-minute walk distance (r=20.38, p,0.01) and MRC (Medical Research Council) grade (r=0.48, p,0.01), and had good stability over time (intraclass correlation coefficient=0.9, p,0.001). Conclusion: Dyspnoea-12 fulfills modern psychometric requirements for measurement. It provides a global score of breathlessness severity that incorporates both"-˜physical" " and"-˜affective" " aspects, and can measure dyspnoea in a variety of diseases.
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Booth S, Bausewein C, Higginson I, Moosavi SH, 'Pharmacological treatment of refractory breathlessness'
Expert Review of Respiratory Medicine 3 (1) (2009) pp.21-36
ISSN: 1747-6348 eISSN: 1747-6356AbstractPublished hereRefractory breathlessness is one of the most common and devastating symptoms of advanced cardiorespiratory disease, both malignant and nonmalignant. In spite of increased interest in research in the last 20 years, there have been few significant advances in the palliation of this distressing condition. The most successful palliative regimens for breathlessness always include pharmacological and nonpharmacological interventions used concurrently. When patients are active, nonpharmacological treatments (e.g., exercise) are the most effective. As the patient becomes more breathless, eventually becoming breathless at rest, pharmacological treatments become more important. Opioids have the most extensive evidence base to guide their use. Other pharmacological interventions may act partly by helping breathlessness (by mechanisms still uncertain) or by treating concomitant precipitating and exacerbating conditions, such as depression and anxiety. A specific treatment to palliate breathlessness remains elusive. The neurophysiological substrate of breathlessness perception is still relatively poorly understood and not well reproduced in animal models. Research using functional MRI and other imaging, with more precise clinical trial methods, may help to bring significant advances. In the next 5 years, novel approaches to delivering opioids may be developed, the effective use of inhaled furosemide may be elucidated and the place of antidepressants and anxiolytics will become clearer. A role for cannabinoids may emerge. New drugs may be developed as our understanding of neurophysiology grows.
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Dorman S, Jolley C, Abernethy A, Currow D, Johnson M, Farquhar M, Griffiths G, Peel T, Moosavi S, Byrne A, Wilcock A, Alloway L, Bausewein C, Higginson I, Booth S, 'Researching breathlessness in palliative care: consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup'
Palliative Medicine 23 (3) (2009) pp.213-227
ISSN: 0269-2163AbstractBreathlessness is common in advanced disease and can have a devastating impact on patients and carers. Research on the management of breathlessness is challenging. There are relatively few studies, and many studies are limited by inadequate power or design. This paper represents a consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup. The aims of this paper are to facilitate the design of adequately powered multi-centre interventional studies in breathlessness, to suggest a standardised, rational approach to breathlessness research and to aid future"between study" comparisons. Discussion of the physiology of breathlessness is included. Palliative MedicinePublished here -
Booth S, Moosavi S, Higginson I, 'The etiology and management of intractable breathlessness in patients with advanced cancer: a systematic review of pharmacological therapy'
Nature Clinical Practice Oncology 5 (2) (2008) pp.90-100
ISSN: 1743-4254AbstractIntractable breathlessness is a common, devastating symptom of advanced cancer causing distress and isolation for patients and families. In advanced cancer, breathlessness is complex and usually multifactorial and its severity unrelated to measurable pulmonary function or disease status. Therapeutic advances in the clinical management of dyspnea are limited and it remains difficult to treat successfully. There is growing interest in the palliation of breathlessness, and recent work has shown that a systematic, evidence-based approach by a committed multidisciplinary team can improve lives considerably. Where such care is lacking it may be owing to therapeutic nihilism in clinicians untrained in the management of chronic breathlessness and unaware that there are options other than endurance. Optimum management involves pharmacological treatment (principally opioids, occasionally oxygen and anxiolytics) and nonpharmacological interventions (including use of a fan, a tailor-made exercise program, and psychoeducational support for patient and family) with the use of parenteral opioids and sedation at the end of life when appropriate. Effective care centers on the patient" s needs and goals. Priorities in breathlessness research include studies on: neuroimaging, the effectiveness of new interventions, the efficacy, safety, and dosing regimens of opioids, the contribution of deconditioning, and the effect of preventing or reversing breathlessness.Published here -
Moosavi SH, Binks AP, Lansing RW, Topulos GP, Banzett RB, Schwartzstein RM, 'Effect of inhaled furosemide on air hunger induced in healthy humans'
Respiratory Physiology & Neurobiology 156 (1) (2007) pp.1-8
ISSN: 1569-9048 eISSN: 1878-1519AbstractPublished hereRecent evidence suggests that inhaled furosemide relieves dyspnoea in patients and in normal subjects made dyspnoeic by external resistive loads combined with added dead-space. Furosemide sensitises lung inflation receptors in rats, and lung inflation reduces air hunger in humans. We therefore hypothesised that inhaled furosemide acts on the air hunger component of dyspnoea. Ten subjects inhaled aerosolized furosemide (40 mg) or placebo in randomised, double blind, crossover experiments. Air hunger was induced by hypercapnia (50 ± 2 mmHg) during constrained ventilation (8 ± 0.9 L/min) before and after treatment, and rated by subjects using a 100 mm visual analogue scale. Subjects described a sensation of air hunger with little or no work/effort of breathing. Hypercapnia generated less air hunger in the first trial at 23 ± 3 min after start of furosemide treatment (58 ± 11% to 39 ± 14% full scale); the effect varied substantially among subjects. The mean treatment effect, accounting for placebo, was 13% of full scale (P = 0.052). We conclude that 40 mg of inhaled furosemide partially relieves air hunger within 1 h and is accompanied by substantial diuresis.
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Moosavi SH, Banzett RB, Butler JP, 'Time course of air hunger mirrors the biphasic ventilatory response to hypoxia'
Journal of Applied Physiology 97 (6) (2004) pp.2098-2103
ISSN: 8750-7587 eISSN: 1522-1601AbstractPublished hereDetermining response dynamics of hypoxic air hunger may provide information of use in clinical practice and will improve understanding of basic dyspnea mechanisms. It is hypothesized that air hunger arises from projection of reflex brain stem ventilatory drive (“corollary discharge”) to forebrain centers. If perceptual response dynamics are unmodified by events between brain stem and cortical awareness, this hypothesis predicts that air hunger will exactly track ventilatory response. Thus, during sustained hypoxia, initial increase in air hunger would be followed by a progressive decline reflecting biphasic reflex ventilatory drive. To test this prediction, we applied a sharp-onset 20-min step of normocapnic hypoxia and compared dynamic response characteristics of air hunger with that of ventilation in 10 healthy subjects. Air hunger was measured during mechanical ventilation (minute ventilation = 9 ± 1.4 l/min; end-tidal Pco2 = 37 ± 2 Torr; end-tidal Po2 = 45 ± 7 Torr); ventilatory response was measured during separate free-breathing trials in the same subjects. Discomfort caused by “urge to breathe” was rated every 30 s on a visual analog scale. Both ventilatory and air hunger responses were modeled as delayed double exponentials corresponding to a simple linear first-order response but with a separate first-order adaptation. These models provided adequate fits to both ventilatory and air hunger data (r2 = 0.88 and 0.66). Mean time constant and time-to-peak response for the average perceptual response (0.36 min−1 and 3.3 min, respectively) closely matched corresponding values for the average ventilatory response (0.39 min−1 and 3.1 min). Air hunger response to sustained hypoxia tracked ventilatory drive with a delay of ∼30 s. Our data provide further support for the corollary discharge hypothesis for air hunger.
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Lansing Robert W, Moosavi Shakeeb H, Banzett Robert B, 'Measurement of dyspnea: word labeled visual analog scale vs. verbal ordinal scale'
Respiratory Physiology & Neurobiology 134 (2) (2003) pp.77-83
ISSN: 1569-9048 eISSN: 1878-1519AbstractPublished hereWe previously used a verbal ordinal rating scale to measure dyspnea. That scale was easy for subjects to use and the words provided consistency in ratings. We have recently developed a word labeled visual analog scale (LVAS) with labels placed by the subjects, retaining the advantages of a verbal scale while offering a continuous scale that generates parametric data. In a retrospective meta-analysis of data from 43 subjects, individuals differed little in their placement of words on the 100 mm LVAS (mean±S.D. for slight=20±2.5 mm, moderate=50±5 mm and severe=80±6 mm) and ratings were distributed uniformly along the scale. A significant stimulus–response correlation was obtained for both the LVAS (r2=0.98) and for the verbal ordinal scale (Spearman r=0.94). The resolution of the two scales differed only slightly. With meaningful verbal anchors, well-defined end-points, and clear instructions about the specific sensation to be rated, both scales provide valid measures of dyspnea.
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Moosavi SH, Golestanian E, Binks AP, Lansing RW, Brown R, Banzett RB, 'Hypoxic and hypercapnic drives to breathe generate equivalent levels of air hunger in humans'
Journal of Applied Physiology 94 (1) (2003) pp.141-154
ISSN: 8750-7587 eISSN: 1522-1601AbstractPublished hereAnecdotal observations suggest that hypoxia does not elicit dyspnea. An opposing view is that any stimulus to medullary respiratory centers generates dyspnea via “corollary discharge” to higher centers; absence of dyspnea during low inspired Po 2 may result from increased ventilation and hypocapnia. We hypothesized that, with fixed ventilation, hypoxia and hypercapnia generate equal dyspnea when matched by ventilatory drive. Steady-state levels of hypoxic normocapnia (end-tidal Po 2 = 60–40 Torr) and hypercapnic hyperoxia (end-tidal Pco 2= 40–50 Torr) were induced in naive subjects when they were free breathing and during fixed mechanical ventilation. In a separate experiment, normocapnic hypoxia and normoxic hypercapnia, “matched” by ventilation in free-breathing trials, were presented to experienced subjects breathing with constrained rate and tidal volume. “Air hunger” was rated every 30 s on a visual analog scale. Air hunger-Pet O2 curves rose sharply at Pet O2 P > 0.05). Hypercapnia had unpleasant nonrespiratory effects but was otherwise perceptually indistinguishable from hypoxia. We conclude that hypoxia and hypercapnia have equal potency for air hunger when matched by ventilatory drive. Air hunger may, therefore, arise via brain stem respiratory drive.
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Moosavi SH, Guz A, Adams L, 'Repeated exercise paired with “imperceptible” dead space loading does not alter V˙eof subsequent exercise in humans'
Journal of Applied Physiology 92 (3) (2002) pp.1159-1168
ISSN: 8750-7587 eISSN: 1522-1601AbstractPublished hereWe employed an associative learning paradigm to test the hypothesis that exercise hyperpnea in humans arises from learned responses forged by prior experience. Twelve subjects undertook a “conditioning” and a “nonconditioning” session on separate days, with order of performance counterbalanced among subjects. In both sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each separated by 5 min of rest. The only difference between sessions was that all the second-to-penultimate runs of the conditioning session were performed with added dead space in the breathing circuit. Cardiorespiratory responses during the first and last runs (the “control” and “test” runs) were compared for each session. Steady-state exercise end-tidal Pco 2 was significantly lower (P= 0.003) during test than during control runs for both sessions (dropping by 1.8 ± 2 and 1.4 ± 3 Torr during conditioning and nonconditioning sessions, respectively). This and all other test-control run differences tended to be greater during the first session performed regardless of session type. Our data provide no support for the hypothesis implicating associative learning processes in the ventilatory response to exercise in humans.
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Binks AP, Moosavi SH, Banzett RB, Schwartzstein RM, '“Tightness” Sensation of Asthma Does Not Arise from the Work of Breathing'
American Journal of Respiratory and Critical Care Medicine 165 (1) (2002)
ISSN: 1073-449X eISSN: 1535-4970AbstractPublished hereAsthma evokes several uncomfortable sensations including increased “effort to breathe” and chest “tightness.” We have tested the hypotheses that “effort” and “tightness” are due to perception of increased work performed by the respiratory muscles. Bronchoconstriction was induced by inhaled methacholine in 15 subjects with mild asthma (FEV1/FVC baseline = 81.9% ± 5.8; bronchoconstriction = 64.0% ± 8.6). To relieve the work of breathing, and thereby minimize activation of respiratory muscle afferents and motor command, subjects were mechanically ventilated. Subjects separately rated effort to breathe and tightness during mechanical ventilation and during spontaneous breathing. Bronchoconstriction produced elevated end-expiratory lung volume (279 ± 62 ml); in a control study, end-expiratory lung volume was increased equally in the absence of bronchoconstriction by increasing end-expiratory pressure. During bronchoconstriction, ratings of effort were greater during spontaneous breathing than during mechanical ventilation (p
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Morrell MJ, Heywood P, Moosavi SH, Stevens J, Guz A, 'Central chemosensitivity and breathing asleep in unilateral medullary lesion patients: comparisons to animal data'
Respiration Physiology 129 (1-2) (2001) pp.269-277
ISSN: 0034-5687AbstractPublished hereThe rostro-ventrolateral medulla (RVLM) is a site of chemosensitivity in animals; such site(s) have not been defined in humans. We studied the effect of unilateral focal lesions in the rostrolateral medulla (RLM) of man, on the ventilatory CO2 sensitivity and during awake and sleep breathing. Nine patients with RLM lesions (RLM group), and six with lesions elsewhere (non-RLM group) were studied. The ventilatory CO2 sensitivity was lower in the RLM compared with the non-RLM group (mean (S.D.), RLM, 1.4 (0.9), non-RLM 3.0 (0.6) L min−1 mmHg−1). In both groups resting breathing was normal. During sleep all RLM patients had frequent arousals, four had significant sleep disordered breathing (SDB), only one non-RLM patient had SDB. Our findings in humans resemble those in animals with focal RVLM lesions. This review provides evidence that in humans there is an area of chemosensitivity in the RLM. We propose that in humans, dorsal displacement of the RVLM area of chemosensitivity in animals, arises from development of the olive plus the consequences of the evolution of the cerebellum/inferior peduncle.
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Moosavi SH, Topulos GP, Hafer A, Lansing RW, Adams L, Brown R, Banzett RB, 'Acute partial paralysis alters perceptions of air hunger, work and effort at constant PCO2 and'
Respiration Physiology 122 (1) (2000) pp.45-60
ISSN: 0034-5687AbstractPublished hereBreathing sensations of AIR HUNGER, WORK and EFFORT may depend on projections of central motor discharge (corollary discharge) to the forebrain. Source of motor drive (brainstem or cortex) may determine what is perceived. To test the effect of changing motor discharge at constant ventilation, we induced partial neuromuscular blockade during hypercapnic hyperpnea (31±9 L min−1; PETCO2=49±2 Torr) and during matched volitional hyperpnea (34±5 L min−1; PETCO2=41±1 Torr). Decline of vital capacity was similar between conditions (39%). Ventilation was unchanged with paralysis, indicating increased respiratory motor drive to maintain hyperpnea. Sensations were rated on a seven point ordinal scale. Median EFFORT and WORK increased 3–3.5 points with paralysis during both forms of hyperpnea (PP
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Banzett RB, Garcia RT, Moosavi SH, 'Simple contrivance “clamps” end-tidal P CO 2 and P O 2 despite rapid changes in ventilation'
Journal of Applied Physiology 88 (5) (2000) pp.1597-1600
ISSN: 8750-7587 eISSN: 1522-1601AbstractPublished hereThe device described in this study uses functionally variable dead space to keep effective alveolar ventilation constant. It is capable of maintaining end-tidalPCO2 andPO2 within ±1 Torr of the set value in the face of increases in breathing above the baseline level. The set level of end-tidal PCO2 or PO2 can be independently varied by altering the concentration in fresh gas flow. The device comprises a tee at the mouthpiece, with one inlet providing a limited supply of fresh gas flow and the other providing reinspired alveolar gas when ventilation exceeds fresh gas flow. Because the device does not depend on measurement and correction of end-tidal or arterial gas levels, the response of the device is essentially instantaneous, avoiding the instability of negative feedback systems having significant delay. This contrivance provides a simple means of holding arterial blood gases constant in the face of spontaneous changes in breathing (above a minimum alveolar ventilation), which is useful in respiratory experiments, as well as in functional brain imaging where blood gas changes can confound interpretation by influencing cerebral blood flow.
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Morrell M J, Heywood P, Moosavi S H, Guz A, Stevens J, 'Unilateral focal lesions in the rostrolateral medulla influence chemosensitivity and breathing measured during wakefulness, sleep, and exercise'
Journal of Neurology, Neurosurgery and Psychiatry 67 (5) (1999) pp.637-645
ISSN: 0022-3050 eISSN: 1468-330XAbstractPublished hereOBJECTIVES The rostrolateral medulla (RLM) has been identified in animals as an important site of chemosensitivity; in humans such site(s) have not been defined. The aim of this study was to investigate the physiological implications of unilateral lesions in the lower brainstem on the control of breathing.
METHODS In 15 patients breathing was measured awake at rest, asleep, during exercise, and during CO2 stimulation. The lesions were located clinically and by MRI; in nine patients they involved the RLM (RLM group), in six they were in the pons, cerebellum, or medial medulla (Non-RLM group). All RLM group patients, and three non-RLM group patients had ipsilateral Horner’s syndrome.
RESULTS Six of the RLM group had a ventilatory sensitivity to inhaled CO2(V˙/PET CO2) below normal (group A:V˙/PET CO2, mean, 0.87; range 0.3–1.4 l.min-1/mm Hg). It was normal in all of the non-RLM group (group B: V˙/PET CO2, mean, 3.0; range, 2.6–3.9 min-1/mmHg). There was no significant difference in breathing between groups during relaxed wakefulness (V˙, group A: 7.44 (SD 2.5) l.min-1; group B: 6.02 (SD 1.3) l.min-1; PET CO2, group A: 41.0 (SD 4.2) mm g; group B: 38.3 (SD2.0) mm Hg) or during exercise (V˙/V˙O2: group A: 21 (SD 6.0) l.min-1/l.min-1; group B: 24 (SD 7.3) l.min-1/l.min-1). During sleep, all group A had fragmented sleep compared with only one patient in group B (group A: arousals, range 13 to > 60 events/hour); moreover, in group A there was a high incidence of obstructive sleep apnoea associated with hypoxaemia.
CONCLUSION Patients with unilateral RLM lesions require monitoring during sleep to diagnose any sleep apnoea. The finding that unilateral RLM lesions reduce ventilatory sensitivity to inhaled CO2 is consistent with animal studies. The reduced chemosensitivity had a minimal effect on breathing awake at rest or during exercise.
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Moosavi SH, Ellaway PH, Catley M, Stokes MJ, Haque N, 'Corticospinal function in severe brain injury assessed using magnetic stimulation of the motor cortex in man'
Journal of the Neurological Sciences 164 (2) (1999) pp.179-186
ISSN: 0022-510X eISSN: 1878-5883AbstractPublished hereWe have assessed corticospinal function in 19 post-coma patients severely brain-injured by anoxia or physical trauma. Eleven patients were unresponsive (Category 1) and eight demonstrated minimal, non-verbal responses to simple commands (Category 2). Motor evoked potentials (MEPs) could be elicited in hand and leg muscles in nine Category 1 and all eight Category 2 patients in response to transcranial magnetic stimulation (TMS). In comparison with normal subjects, threshold to TMS was significantly elevated in Category 1 but not in Category 2. Central conduction times were within the normal range except for two patients (one in each category) in whom they were prolonged. The variability in MEP amplitude to constant TMS was not significantly different from normal in either category. The size of MEPs recorded simultaneously in different hand muscles were correlated in all three groups. The presence of H-reflexes in hand muscles was associated with an absence of MEPs or a high threshold to TMS. Variability of MEPs was substantially greater than that of H-reflexes. We conclude that brain injury of a severity that may preclude consciousness and voluntary movement does not invariably predicate a non-functional motor cortex and corticospinal system.
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Wuyam B, Moosavi SH, Decety J, Adams L, Lansing RW, Guz A, 'Imagination of dynamic exercise produced ventilatory responses which were more apparent in competitive sportsmen'
The Journal of Physiology 482 (3) (1995) pp.713-724
ISSN: 0022-3751 eISSN: 1469-7793AbstractPublished here1. The cardiorespiratory response to imagination of previously performed treadmill exercise was measured in six competitive sportsmen and six non-athletic males. This was compared with the response to a control task (imaging letters) and a task not involving imagination (‘treadmill sound only’). 2. In athletes, imagined exercise produced increases in ventilation which varied within and between subjects. The mean maximal increase (11.71 min-1) was approximately 20% of the ventilatory response to actual exercise. This was primarily due to treadmill speed-related increases in respiratory frequency (mean maximal increase, 14.8 breaths min-1) and resulted in significant reductions in end-tidal PCO2 (mean maximal fall, 7 mmHg). These effects were greater (P 0.2). 4. In non-athletes, imagination of exercise produced no changes in cardiorespiratory variables. No significant differences were detected in subjective assessments of movement imagery ability between athletes and non-athletes (P = 0.17). 5. This study demonstrates that ventilatory effects, when observed, are specific to imagination of exercise. The greater likelihood of generating ventilatory responses in highly trained athletes, experienced in ‘rhythmic’ sports, may be related to awareness of breathing and its role in exercise imagination strategy. A volitional component of the response cannot be discounted.
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Beardsmore CS, Macfadyen UM, Moosavi SH, Wimpress SP, Thompson J, Simpson H, 'Measurement of lung volumes during active and quiet sleep in infants'
Pediatric Pulmonology 7 (2) (1989) pp.71-77
ISSN: 8755-6863 eISSN: 1099-0496AbstractPublished hereThe question of whether functional residual capacity (FRC) falls in infants during active sleep has been clouded by studies using different subject groups and techniques for measurements of lung volume and determination of sleep state. Twenty healthy full-term infants within the first week of life participated in the present study. Neurophysiological and behavioral criteria were used to define sleep state, and measurements of FRC were made using a specially constructed closed-circuit helium dilution system. Regularity of respiration was recorded using magnetometers on the chest and a modified respirator monitor. Results showed that no significant changes in FRC occurred, related either to sleep state or to regularity of respiration. In addition, we failed to detect any differences in FRC between the sexes.
Book chapters
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Ellaway PH, Moosavi SH, Stokes MJ, Catley M, Haque N, 'Chapter 44 Indices of Cortical Motor Function Following Severe Brain Injury In man' in Chapter 44 Indices of Cortical Motor Function Following Severe Brain Injury In man, Elsevier (1999)
ISSN: 0079-6123 eISSN: 1875-7855AbstractPublished hereThis chapter assesses the degree to which the function of the corticospinal tract and the motor cortex in man is affected by severe brain injury of a severity that results in a lack of purposeful movements and no apparent awareness of the self or surroundings. The subjects mentioned in the chapter had suffered either anoxic or traumatic (possibly including anoxia) brain injury that resulted initially in an indefinite period of coma. On emergence from coma, a group of the subjects assumed sleep/wake cycles, with eyes open during the awake periods, but they exhibited no purposeful movements and showed no signs of awareness to a wide range of sensory stimuli. Such a condition is usually referred to as “persistent vegetative state” or “apallic syndrome.” Certain attributes of transcranial magnetic stimulation (TMS), as a method for eliciting a corticospinal output from the motor cortex, suggest that the technique may allow the level of excitability of the motor cortex to be assessed. TMS excites corticospinal neurons transynaptically, or at least at the initial segment. Only at higher strengths, well above the threshold and at specific orientations of the magnetic coil, does direct stimulation of corticospinal axons occur. TMS also activates cortical inhibitory circuits. Thus, the stimulation of corticospinal neurons by TMS is likely to be influenced by concurrently active pre-synaptic inputs.
Other publications
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Grogono JC, Pattinson KTS, Moosavi SH, 'Debating pharmacological options for dyspnoea relief; the need for full, accurate and balanced critical appraisal of the evidence [letter to the editor]', (2019)
Published here Open Access on RADAR
Professional information
Memberships of professional bodies
- Physiological Society (Full member)
- The Dyspnea Society (Nominee for executive committee)
Conferences
- Dyspnea 2021 International Conference - Hosted at Oxford Brookes in July 2022
Further details
The Frontiers in Neuroscience jounal invited us to guest-edit a special collection of articles on Respiratory control and dysfunction in neurological patients. Please follow this link to submit your papers.
Other experience
- 1987-1988 Res Technician (Leicester Royal infirmary-Child Health)
- 1988-1994 Clinical Physiologist (Charing Cross Hospital, London)
- 1994-1998 PostDoc RA (Imperial College London-Neurophysiology)
- 1998-2003 Research Scientist (Harvard School of Public Health)
- 2004-2010 Lecturer (Imperial College London-NHLI)
- 2010-2011 Research Scientist (Stoke Mandeville Hospital-UKSCIRN)
Further information