Physiological mechanisms of lung volume reduction coils in emphysema

Emphysema is characterised by airflow limitation that is a result of both loss of elastic recoil and small airways disease. It is poorly responsive to medical therapy. Lung volume reduction coils improve symptoms and lung function in the short term. However their mechanism of action and medium term effectiveness is not fully understood. Methods A randomised controlled study consisting of thirty patients with severe chronic obstructive pulmonary disease was performed. Control patients crossed over to the treatment arm at 12 months. The primary outcome was 6 minute walk distance at 12 months. Changes in spirometry, lung volumes, computed tomography measured lung volumes and gas trapping were also assessed. In a small subgroup of patients detailed physiological characterization was performed to assess changes in airways resistance, ventilation heterogeneity and lung elastic recoil. Results In the randomised study at 12 months, there was no significant difference in 6 minute walk distance between treatment and controls (between group difference 25m, 95% CI -40 to 59, p = 0.7028). There was a trend to improvement in symptoms measured by SGRQ score (-6.53 points, 96% CI -17 to 0.2, p = 0.0589) and significant improvements in FRC (-0.41L, 95% CI -0.86 to -0.1, p = 0.0077). Including the crossovers there were 4 patient deaths (13.3%). Target lobe volume at both inspiration and expiration was reduced with no overall change in gas trapping. Airways resistance by plethysmography did not change significantly. There was no significant change in elastic recoil. Conclusions Treatment with lung volume reduction coils is effective at reducing lung volume and may achieve its effect through volume loss. There could also be an effect through elastic recoil as there was a non-significant trend towards an increase after the intervention. There appears to be no effect on airways resistance. Careful patient selection is required as there is a risk of death following treatment.Open Acces

Bioimpedance spectroscopy - can it be used as a tool for monitoring fluid shifts in burns?

Large fluid shifts and oedema are features of burn injuries. Oedema hampers burn wound healing and is directly related to the size and depth of the burn. The degree of oedema in burns covers a broad spectrum: Minor burns cause localised or peripheral oedema, whilst major burns may result in a systemic inflammatory response which can be life threatening and necessitates formal fluid resuscitation. Acute burn fluid resuscitation is paramount in decreasing patient morbidity and mortality but can contribute to already large amounts of oedema. There is currently no single clinically applicable, non-invasive and accurate outcome measure to titrate fluid volumes in acute burns or monitor the effect of treatments on oedema (in minor and major burns). Bioimpedance spectroscopy (BIS) has emerged as a possible solution to these challenges. It can measure body fluid compartments and thus fluid volume changes over time providing a sensitive non-invasive device to estimate resuscitation requirements and oedema change and is emerging as a measure of wound healing. This series of studies therefore aimed to 1) address the potential barriers to use of BIS in the burns population, 2) determine if BIS provides an accurate measure of whole body/systemic fluid volume change and 3) localised burn wound oedema changes, as applied across the spectrum of burn severity, and 4) determine if BIS can monitor wound healing in minor burns. The studies therefore investigated novel whole body and localised electrode positions in the presence of open and dressed wounds, using repeated measures over time in minor and major burns. The key novel findings arising from the research series include: 1) alternate electrode placements are interchangeable with standardised placement for the measurement of whole body resistance, extracellular and total body fluid volumes in specified dressing conditions. Therefore BIS can be utilised to monitor changes in fluid shifts when wounds preclude the manufacturer’s standard placement of electrodes in the presence of burn wounds, 2) BIS is a reliable method of monitoring fluid in any dressing condition and electrode position with no systematic bias indicated in both major and minor burns, 3) In both minor and major burns, BIS is a valid indicator of net fluid shifts and oedema change, if dressing condition is adjusted for using the developed algorithms or calculator and 4) BIS resistance variables, R0 and Rinf, can be used to monitor wound healing in minor limb burns as an adjunct to standard practice

Aerospace Medicine and Biology: A continuing bibliography (supplement 160)

This bibliography lists 166 reports, articles, and other documents introduced into the NASA scientific and technical information system in October 1976

Impact of surgical and of bronchoscopic lung volume reductions in patients with emphysema and hyperinflation on lung structure, function and inflammation

Background – A robust biomarker for predicting and evaluating the response to lung volume reduction (LVR) interventions remains elusive. We investigated the hypothesis that LVR will be accompanied by measurable changes in novel indices of lung structure, function, and inflammation that can be correlated with changes to the conventional clinical parameters and that reliable identifiers of baseline predictors of therapeutic response (minimal clinically important difference, MCID, of at least 10% reduction of residual volume) will be identified. Methods – 72 consecutive subjects with severe emphysema and hyperinflation scheduled for lung volume reductions were recruited: lung volume reduction surgery (LVRS) – 15; Endobronchial valve (EBV) – 29, Endobronchial coil (EBC) – 28. All underwent detailed clinical phenotyping comprising demographics, symptom scores, computed tomography imaging, exercise capacity and lung function measurements during exacerbation-free periods at baseline and at three months after intervention. Novel techniques including quantitative computed tomography (qCT), impulse oscillometry (IOS) and multiple breath nitrogen washout (MBNW), and microvesicle quantification were employed to assess changes in lung structure, function and inflammation, respectively. Results – Surgery achieved the greatest lung volume reductions, △residual volume (RV) of -1.26 ± 0.58 litres (p<0.01), and more than 90% of recipients met the MCID of ≥10% RV reduction. It was the only intervention to be accompanied by improvements in functional gas trapping on CT, IOS expiratory airways resistance at 5Hz, expiratory and within-breath reactance at 5Hz, and peripheral resonant frequency, attributable to recovery of small airways function. Valve implantations reduced residual volume by -0.91 ± 0.66 litres (p<0.01) and 62% of recipients attained the MCID of ≥10% RV reduction. This was in addition to a smaller reduction in IOS expiratory and within-breath reactance at 5Hz without an accompanying signal in resistance, resonant frequency, or functional gas trapping on CT. Modest improvements to alveolar gas mixing (AME) and small airways function (Sacin) were measured using MBNW in a subset of patients. These data suggest the impact of valves on the peripheral airway compartment was less pronounced than with surgery and was achieved predominantly by deflation of emphysematous lung tissue and restoration of the mechanical pump. Coil implantations resulted in modest volume reductions, △residual volume of -0.31 ± 0.60L (p=0.01): Only 35% of subjects achieved the MCID of ≥10% RV reduction. Three-month physiological outcomes were similarly disappointing with improvements limited to CT-intraparenchymal blood vessel volume (perhaps due to greater radial traction exerted by the coils on the surrounding parenchyma) and the area under reactance during expiration (AXex) on IOS. The comparatively minor degree of volume reduction achieved (and the fall in gas transfer) using this technique may explain the relatively small impact on peripheral airways function. An inflammatory sub-study identified a variety of microvesicle (MV) populations in bronchoalveolar lavage fluid (BALF) and in the plasma of patients with mild to very severe COPD. Of these, polymorphouclear (neutrophil)-derived MVs were found to be substantially increased in BALF and their numbers correlated with airflow limitation, reduced exercise capacity, impaired of quality of life, and the BODE index. BALF neutrophil-derived MVs correlated with BALF neutrophil cell numbers but not with circulating neutrophil MV numbers, implying local alveolar release rather than translocation from the circulation. BALF neutrophil-derived MVs were also shown to be a more robust biomarker of disease severity than BALF neutrophil cell and cytokine levels. In a subset of valve and coil recipients, BALF-neutrophil derived MV levels were evaluated before and after intervention. Mean volume reduction in the coil recipients was exceeded threefold by that of the valve beneficiaries. Unexpectedly there was no statistically significant change in MV numbers at three months in the valve arm. Possible explanations include contamination from more proximal airway sampling / spill over from the ipsilateral lobe(s) or induction of a localised inflammatory response to biofilm formation overlying the nitinol-silicone implants. In contrast, a statistically significant fall in MV numbers was observed in the coil cohort in the absence of clinically meaningful volume reduction. It must however be borne in mind that despite the thin profile of the nitinol endobronchial coil, the surface area of the airway epithelium exposed to sampling is reduced. There were no identifiable predictors of therapeutic response among the novel indices of lung structure, function, and inflammation analysed. Conclusions – The degree of lung volume reduction achieved is critical in determining favourable clinical outcomes for patients with severe emphysema and hyperinflation. Similarly, the structural and functional impacts of lung volume reduction on the small airways compartment, the principal site of airflow obstruction, are proportional to the degree of volume reduction achieved (surgery > valves > coils). The impact of these therapies on airways inflammation requires further scrutiny. qCT and IOS qualify as structural and functional biomarkers, respectively, for evaluating volume reduction – however, their predictive value for therapeutic response is not established from this small dataset. BALF neutrophil-derived MV observations are potentially useful contributors to disease phenotyping alongside lung function tests and qCT imaging – their role as biomarkers for predicting and assessing therapeutic response remains to be seen. Larger randomised controlled trial designs are recommended to further investigate these preliminary findings.Open Acces

Characterisation of exacerbations in non-CF Bronchiectasis to establish endpoints in measuring treatment efficacy

Bronchiectasis is characterised by chronic cough productive of mucopurulent sputum and frequent exacerbations. We have aimed to validate clinical, biochemical and microbiological endpoints to aid planning of future interventional studies. We recruited fifty-eight subjects with bronchiectasis at the Lung Defence unit (Papworth Hospital, Cambridge) and studied them in stable state (no exacerbation in the preceding four weeks) and during an exacerbation over a period of two years. The results of our research are discussed in this study. Clinical symptoms: Cough chest pain, chest discomfort, colour and volume of sputum and fatigue measured by a visual analogue score are useful endpoints. Breathlessness is a reliable endpoint when measured using either a visual analogue score or modified Borg’s breathlessness score. Health related quality of life measured using the Euroqol questionnaire is a sensitive marker of change during an exacerbation. The St George’s respiratory questionnaire did not demonstrate a significant change during an exacerbation. Spirometry: Forced expiratory volume in the first second (actual and percentage predicted) and Forced vital capacity (percentage predicted) do not change during the course of an exacerbation. Forced vital capacity actual may be used as an endpoint. pH of exhaled breath condensate in bronchiectasis is lower than in healthy subjects but does not change during the course of an exacerbation. Sputum appearance is a valid endpoint while 24hour volume of sputum and microbial clearance and anti-pseudomonal antibody titres cannot be used. ESR and serum titres of IFN-γ, TNF-α IL-6, IL-8, IL-10, IL-17 and IL-1β and titres in sputa of IFN-γ, IL-6, IL-17 do not change during an exacerbation. C-reactive protein and titres in sputa of TNF-α, IL-8 and IL-1β are effective indicators and can be recommended for use as end points in therapeutic interventional trial