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BSc, PhD, FHEA
Department of Biological and Medical Sciences
Faculty of Health and Life Sciences
Charlotte Golding -PhD Groome Studentship (Director of Studies)
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.
Objective. 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.
The 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 , much like those identified for pain perception . 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 .
Background. 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.
Objective: 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.
Rationale: 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.
Garner DM, van Leeuwen P, Grönemeyer D, Moosavi S “Assessment of fetal development by HRV and chaotic global techniques.” J Hum Growth Dev. 2016; 26(2): 162-173
1987-1988 Res Technician (Leicester Royal infirmary-Child Health)
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 before starting my current post.