Shakeeb H. Moosavi

Quantification of dyspnoea using descriptors: development and initial testing of the Dyspnoea-12

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 (χ2 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 = −0.38, 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.

The etiology and management of intractable breathlessness in patients with advanced cancer: a systematic review of pharmacological therapy

Intractable 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 patients 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.

Researching breathlessness in palliative care: consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup.

Breathlessness 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.

The time-course of cortico-limbic neural responses to air hunger.

Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak <30s and (2) slow, BOLD signal peak >40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research.

Cannabinoid effects on ventilation and breathlessness: A pilot study of efficacy and safety

Based 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.

Low-Level Carbon Monoxide Exposure Affects BOLD FMRI

Blood 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 constitutes a significant confound in neuroimaging and clinical trials. Low-level (6ppm exhaled) CO effects on BOLD signal 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. CO significantly dampened global BOLD FMRI signal during hypercapnia and visual cortex activation during visual stimulation. During fingertapping, CO reduced visual cortex activation but increased premotor cortex activation. Behavioural and physiological measures remained unchanged. We conclude that BOLD FMRI is vulnerable to CO, possibly through baseline increases in CBF, and suggest exercising caution when imaging populations exposed to elevated CO levels, e.g. with high smoking prevalence.