Publications
112 results found
Hughes JMB, 2021, Medical breakthroughs: chance and opportunity., QJM, Vol: 114, Pages: 229-231
Medical advances of great importance in improving diagnosis, treatment or prevention of disease are often called 'breakthroughs'. The processes by which breakthroughs are achieved are multiple, but may include necessity (a problem which must be solved), opportunity (the time must be right), chance (the unexpected), curiosity (a desire to understand mechanisms) and ingenuity (ability to find a solution). Discovery can be the start of a chain reaction, so that the breakthrough at the end of the chain becomes "inevitable". Two examples are given in which these attributes played a part (i) the development of a vaccine against the poliomyelitis virus and (ii) the harnessing of penicillin as a therapeutic agent to treat serious bacterial infections.
Shovlin CL, Hughes JMB, Allison DJ, et al., 2018, Outcomes of patients with pulmonary arteriovenous malformations considered for lung transplantation, Publisher: SPRINGER, Pages: 163-163, ISSN: 0969-6970
Shovlin CL, Buscarini E, Hughes JMB, et al., 2017, Long-term outcomes of patients with pulmonary arteriovenous malformations considered for lung transplantation, compared with similarly hypoxaemic cohorts, BMJ Open Respiratory Research, Vol: 4, ISSN: 2052-4439
INTRODUCTION:Pulmonary arteriovenous malformations (PAVMs) may not be amenable to treatment by embolization or surgical resection, and many patients are left with significant hypoxemia. Lung transplantation has been undertaken.There is no guidance on selection criteria.METHODS:To guidetransplantation listingassessments, the outcomes of the six patients who had been considered for transplantation were compared to a similarly hypoxemic patient group recruited prospectively between2005-2016at thesame UK institution.RESULTS: Sixpatientshad been formally considered for lung transplantation purely for PAVMs. One underwent a single lung transplantation for diffuse PAVMs and died within 4 weeks of surgery. Theother five were not transplanted, in four cases at the patients’ request.Their current survival ranges from 16-27 (median 21) years post transplant assessment. Of 444 consecutive patients with PAVMs recruited between 2005-2016, 42 were similarly hypoxemic to the “transplant-considered”cohort (SaO2 <86.5%). Hypoxemic cohorts maintained arterial oxygen content through secondary erythrocytosis and higher haemoglobin. The “transplant-considered” cohort had similar CaO2to the hypoxemic comparator group,but higher MRC dyspnea scores(p=0.023),higher rates of cerebral abscesses (p=0.0043) and higher rates of venous thromboemboli (p=0.0009) that were evident before and after the decision to list for transplantation. CONCLUSIONS: The non-transplanted patients demonstrated marked longevity. Symptoms and co-morbidities were better predictors of health than oxygen measurements. While a case-by-case decision, weighing survival estimates and quality of life will help patients in their decision making, the data suggesta verystrong case must be made before lung transplantation is considered.
Borland C, Hughes JMB, Guénard H, 2017, The blood transfer conductance for CO and NO., Respir Physiol Neurobiol, Vol: 241, Pages: 53-57
Nitric oxide was introduced over 30 years ago as a test gas for alveolar capillary diffusion. As for CO its transfer has been interpreted according to the Roughton Forster relationship: 1/DL=1/DM+1/θVc. There has been disagreement, since the first measurements of DLNO, over whether θNO is infinite and thus DLNO=DMNO. There is overwhelming in vitro evidence that θNO is finite yet several groups (Coffman et al., 2017; Tamhane et al., 2001) use an infinite value in vivo. They also assume that DMNO is greater than twice DMCO, making DMCO less than that predicted by the physical laws of diffusion. Finally some (Coffman et al., 2017) recommend use of Reeve and Park's value for θCO (Reeves and Park, 1992; Coffman et al., 2017) rather than Forster's (Forster, 1987). Their grounds for doing so are that the combination of an infinite theta NO, an empirical value for DMNO/DMCO (>2.0) and Reeve and Park's θCO gives a value of DMCO (using a combined DLNO-DLCO analysis) which agrees with the DMCO value calculated separately by the classical two-stage oxygen technique of Roughton and Forster. In this paper we examine whether there are physiological reasons for assuming that DMNO is over twice DMCO in vivo. We are critical of Reeves and Park's estimate for the 1/θCO-PO2 relationship. We review in vitro estimates of θCO in the light of Guenard et al.'s recent in vivo estimate.
Hughes JMB, Dinh-Xuan AT, 2017, The DLNO/DLCO ratio: Physiological significance and clinical implications., Respir Physiol Neurobiol, Vol: 241, Pages: 17-22
DLNO/DLCO directly measures the ratio of the diffusing capacities of the lung for nitric oxide (NO) and carbon monoxide (CO). In terms of the Roughton and Forster (1957) equation, 1/DL=1/Dm+1/θVc, where Dm is the membrane (Dm) and θVc is the red cell component of the overall diffusing conductance (DL); DLNO mostly reflects the Dm component and DLCO the θVc red cell component. The DLNO/DLCO ratio is positively related to the DmCO/Vc ratio and the CO red cell resistance (1/θCOVc) as a percentage of the total resistance (1/DLCO), independent of the absolute values of DLNO or DLCO. In clinical studies, a raised DLNO/DLCO ratio (≥110% predicted versus a control group), plus a low DLNO and DLCO (<67% pred), predicts pulmonary vascular disease, while a low DLNO/DLCO ratio, with similarly reduced DLNO and DLCO, is associated with interstitial lung disease with fibrosis. More clinical studies are needed, and reference values need to be better defined.
Rizvi A, Macedo P, Babawale L, et al., 2017, Hemoglobin Is a Vital Determinant of Arterial Oxygen Content in Hypoxemic Patients with Pulmonary Arteriovenous Malformations., Annals of the American Thoracic Society, Vol: 14, Pages: 903-911, ISSN: 2329-6933
RATIONALE: Arterial partial pressure of oxygen (PaO2), and oxygen saturation (SaO2) are commonly measured in respiratory practice, but arterial oxygen content (CaO2) refers to the volume of oxygen delivered to the tissues per unit blood volume. CaO2 is calculated from SaO2 and the hemoglobin concentration in blood, recognizing that each gram of hemoglobin can transport approximately 1.34mls of oxygen when fully saturated. OBJECTIVES: To prospectively evaluate serial changes in CaO2 in man, incorporating and excluding dynamic changes to oxygenation and hemoglobin parameters that may occur during life. METHODS: A cohort of 497 consecutive patients at risk of both hypoxemia and anemia were recruited. The patients had radiologically-proven pulmonary arteriovenous malformations (PAVMs) which result in hypoxemia due to right-to-left shunting, and concurrent hereditary hemorrhagic telangiectasia (HHT) which placed them at risk of iron deficiency anemia due to recurrent hemorrhagic iron losses. Presentation SaO2 (breathing room air, by pulse oximetry), hemoglobin, red cell and iron indices were measured, and CaO2 calculated by SaO2*hemoglobin*1.34mls/gram. Serial measurements were evaluated in 100 cases spanning up to 32.1 (median 10.5) years. RESULTS: Presentation CaO2 ranged from 7.6-27.5 (median 17.6) mls/dL. CaO2 did not change appreciably across the SaO2 quartiles. In contrast, hemoglobin ranged from 5.9-21.8g/dL (median 14.1g/dL), with a linear increase in CaO2 across hemoglobin quartiles. Following PAVM embolization and an immediate increase in SaO2, hemoglobin fell and CaO2 was unchanged 1.6-12 (median 4) months later. When hemoglobin fell due to iron deficiency, there was no change in SaO2. Similarly, when hemoglobin rose after iron treatment, there was no change in SaO2, and the expected CaO2 increment was observed. These relationships were not evident during pregnancy when hemoglobin fell, and PAVMs usually deteriorated: In pregnancy SaO2 commonly increased, and
Zavorsky GS, Hsia CCW, Hughes JMB, et al., 2017, Standardisation and application of the single-breath determination of nitric oxide uptake in the lung., Eur Respir J, Vol: 49
Diffusing capacity of the lung for nitric oxide (DLNO), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breath DLNO This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar "collection" or continuously sampled via rapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4-6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40-60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension (PAO2 ) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min-1·mmHg-1·mL-1 of blood; 6) the equation for 1/θCO should be (0.0062·PAO2 +1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holding PAO2 and adjusted to an average haemoglobin concentration (male 14.6 g·dL-1, female 13.4 g·dL-1); 7) a membrane diffusing capacity ratio (DMNO/DMCO) should be 1.97, based on tissue diffusivity.
Shovlin CL, Hughes JMB, Layton M, et al., 2016, LONG TERM OUTCOMES FOR PATIENTS WITH PULMONARY ARTERIOVENOUS MALFORMATIONS CONSIDERED FOR LUNG TRANSPLANTATION, British Thoracic Society Winter Meeting 2016, Publisher: BMJ PUBLISHING GROUP, Pages: A101-A101, ISSN: 0040-6376
Rizvi A, Babawale L, Hughes JMB, et al., 2016, Effect of age on arterial oxygen content in patients with pulmonay arteriovenous malfomations, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Hughes JMB, 2015, Hypoxic pulmonary vasoconstriction: clinical implications., European Respiratory Journal, Vol: 47, Pages: 31-34, ISSN: 0903-1936
HPV is an adaptation for fetal development and affords some advantage in optimising gas exchange in adults http://ow.ly/Uh54oHypoxic pulmonary vasoconstriction (HPV) and its mechanism of action continue to be of great interest to clinicians and physiologists. Sommer et al. [1] have reviewed HPV in this issue of the European Respiratory Journal. The literature is so extensive that another recent comprehensive review contained 2229 references [2].
Rizvi AF, Babawale L, Hughes JMB, et al., 2015, THE EFFECT OF AGE ON ARTERIAL OXYGEN CONTENT IN PATIENTS WITH PULMONARY ARTERIOVENOUS MALFORMATIONS (PAVMS), Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A32-A33, ISSN: 0040-6376
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Hughes JMB, Borland CDR, 2015, The centenary (2015) of the transfer factor for carbon monoxide (T(LCO)): Marie Krogh's legacy., Thorax, Vol: 70, Pages: 391-394
Howard LSGE, Santhirapala V, Murphy K, et al., 2014, Cardiopulmonary Exercise Testing Demonstrates Maintenance of Exercise Capacity in Patients With Hypoxemia and Pulmonary Arteriovenous Malformations, CHEST, Vol: 146, Pages: 709-718, ISSN: 0012-3692
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- Citations: 18
Hughes JMB, van der Lee I, 2014, The T(LNO)/T(LCO) ratio in pulmonary function test interpretation., Eur Respir J, Vol: 43
Santhirapala V, Howard LSG, Murphy K, et al., 2013, DYSPNEA AND EXERCISE CAPACITY ARE NOT RELATED TO ARTERIAL HYPOXEMIA IN THE ABSENCE OF ALVEOLAR HYPOXIA: PROSPECTIVE STUDIES IN PATIENTS WITH PULMONARY ARTERIOVENOUS MALFORMATIONS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A24-A24, ISSN: 0040-6376
Hughes JMB, 2013, Invited editorial on "Lung membrane conductance and capillary volume derived from the NO and CO transfer in high altitude newcomers"., J Appl Physiol (1985), Vol: 115, Pages: 153-154
Hughes JMB, van der Lee I, 2013, The TL,NO/TL,CO ratio in pulmonary function test interpretation., Eur Respir J, Vol: 41, Pages: 453-461
The transfer factor of the lung for nitric oxide (T(L,NO)) is a new test for pulmonary gas exchange. The procedure is similar to the already well-established transfer factor of the lung for carbon monoxide (T(L,CO)). Physiologically, T(L,NO) predominantly measures the diffusion pathway from the alveoli to capillary plasma. In the Roughton-Forster equation, T(L,NO) acts as a surrogate for the membrane diffusing capacity (D(M)). The red blood cell resistance to carbon monoxide uptake accounts for ~50% of the total resistance from gas to blood, but it is much less for nitric oxide. T(L,NO) and T(L,CO) can be measured simultaneously with the single breath technique, and D(M) and pulmonary capillary blood volume (V(c)) can be estimated. T(L,NO), unlike T(L,CO), is independent of oxygen tension and haematocrit. The T(L,NO)/T(L,CO) ratio is weighted towards the D(M)/V(c) ratio and to α; where α is the ratio of physical diffusivities of NO to CO (α=1.97). The T(L,NO)/T(L,CO) ratio is increased in heavy smokers, with and without computed tomography evidence of emphysema, and reduced in the voluntary restriction of lung expansion; it is expected to be reduced in chronic heart failure. The T(L,NO)/T(L,CO) ratio is a new index of gas exchange that may, more than derivations from them of D(M) and V(c) with their in-built assumptions, give additional insights into pulmonary pathology.
Hughes JMB, Pride NB, 2013, Hooray for the V<sub>A</sub>/TLC and DL<sub>CO</sub>/V<sub>A</sub> Reply, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 187, Pages: 107-107, ISSN: 1073-449X
Hughes JMB, Pride NB, 2012, Examination of the Carbon Monoxide Diffusing Capacity (DL<sub>CO</sub>) in Relation to Its Kco and VA Components, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 186, Pages: 132-139, ISSN: 1073-449X
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- Citations: 158
Wechalekar K, Underwood SR, Hughes JMB, 2012, Nuclear imaging in pulmonary sarcoidosis, Sarcoidosis, Editors: Mitchell, Wells, Spiro, London, Publisher: Hodder Arnold, Pages: 142-149
Wechalekar K, Underwood SR, Hughes JMB, 2012, Radionuclide imaging in cardiac sarcoidosis, Sarcoidosis, Editors: Mitchell, Wells, Spiro, Moller, London, Publisher: Hodder Arnold, Pages: 180-184
Hughes JMB, 2009, Let's find out the size of these "shunts"., J Appl Physiol (1985), Vol: 107, ISSN: 8750-7587
Hughes JM, West JB, 2008, Point–Counterpoint: Gravity is/is not the major factor determining the distribution of blood flow in the human lung, Journal of Applied Physiology, Vol: 104, Pages: 1531-1540
Hughes JMB, 2007, Assessing gas exchange., Chron Respir Dis, Vol: 4, Pages: 205-214, ISSN: 1479-9723
In clinical practice there are two sorts of measurements, a) arterial oxygen and carbon dioxide partial pressure (PaO2, PaCO2) or arterial oxygen saturation (SaO2), and b) the transfer capacity for carbon monoxide (TLCO). The former measures the output or performance of the lung as a gas exchanger, and the latter estimates the available surface area or potential for gas exchange. As gas exchange deteriorates (PaO2 falls and PaCO2 rises), the body compensates by increasing ventilation and lowering PaCO2). Therefore, a high PaCO2 represents chronic respiratory or "compensation" failure, either chemo-insensitivity ("won't breathe") or neuromuscular weakness/increased work of breathing ("cannot breathe"). Chronic respiratory failure may progress to acute failure in which PaCO2 falls and PaCO2 rises progressively, assisted ventilation is usually required. The TLCO is a laboratory test which measures the integrity of the blood-gas barrier, it is particularly useful in the assessment of emphysema, interstitial disease and pulmonary vascular disease.
Hodson A, Graham A, Hughes JM, et al., 2006, Pulmonary-artery-to-artery anstomoses: angiographic demonstration in patients with chronic thromboembolic pulmonary hypertension, Clinical radiology, Vol: 61, Pages: 259-263
Macedo P, Hughes JMB, Jackson JE, et al., 2004, Maternal risks of pregnancy in patients with pulmonary arteriovenous malformations, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: 87-87, ISSN: 0040-6376
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Hughes JMB, Bates DV, 2003, Historical review: the carbon monoxide diffusing capacity (DLCO) and its membrane (DM) and red cell (Theta.Vc) components., Respir Physiol Neurobiol, Vol: 138, Pages: 115-142, ISSN: 1569-9048
The single breath carbon monoxide diffusing capacity (DLCO sb), also called the transfer factor (TLCO), was introduced by Marie and August Krogh in two papers (Krogh and Krogh, Skand. Arch. Physiol. 23, 236-247, 1909; Krogh, J. Physiol., Lond. 49, 271-296, 1915). Physiologically, their measurements showed that sufficient oxygen (by extrapolation from CO) diffused passively from gas to blood without the need to postulate oxygen secretion, a popular theory at the time. Their DLCO sb technique was neglected until the advent of the infra-red CO meter in the 1950s. Ogilvie et al., J. Clin. Invest. 36, 1-17, 1957 published a standardized technique for a 'modified Krogh' single breath DLCO, which eventually became the method of choice in pulmonary function laboratories. The Roughton-Forster equation (J. Appl. Physiol. 1957, 11, 290-302) was an important step conceptually; it partitioned alveolar-capillary diffusion of oxygen (O2) and carbon monoxide (CO) into a membrane component (DM) and a red cell component (theta.Vc) where theta is the DLCO (or DL(O2)) per ml of blood (measured in vitro), and Vc is the pulmonary capillary volume. This equation was based on the kinetics of O2 and CO with haemoglobin (Hb) in solution and with whole blood Hartridge and Roughton, Nature, 1923, 111, 325-326; Proc. R. Soc. Lond. Ser. A, 1923, 104, 376-394; (Proc. R. Soc. Lond. Ser. B, 1923, 94, 336-367; Proc. R. Soc. Lond. Ser. A 1923, 104, 395-430; J. Physiol., Lond. 1927, 62, 232-242; Roughton, Proc. R. Soc. Lond. Ser. B 1932, 111, 1-36) and on the relationship between alveolar P(O2) and 1/DLCO. Subsequently, the relationship between DL(O2) (Lilienthal et al., Am. J. Physiol. 147, 199-216, 1946) and DL(CO) was defined. More recently, the measurement of the nitric oxide diffusing capacity (DLNO) has been introduced. For DL(O2) and DLNO the membrane component (as 1/DM) is an important part of the overall diffusion (transfer) resistance. For the DLCO, 1/theta.Vc probably plays the greater role
Hughes JMB, Pride NB, 2003, Carbon monoxide transfer coefficient (transfer factor/alveolar volume) in females <i>versus</i> males, EUROPEAN RESPIRATORY JOURNAL, Vol: 22, Pages: 186-187, ISSN: 0903-1936
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Easey AJ, Wallace GMF, Hughes JMB, et al., 2003, Should asymptomatic patients with hereditary haemorrhagic telangiectasia (HHT) be screened for cerebral vascular malformations? Data from 22,061 years of HHT patient life, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 74, Pages: 743-748, ISSN: 0022-3050
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Hughes JMB, 2003, The single breath transfer factor (Tl,co) and the transfer coefficient (Kco): a window onto the pulmonary microcirculation., Clin Physiol Funct Imaging, Vol: 23, Pages: 63-71, ISSN: 1475-0961
The transfer factor, Tl,co (with the transfer coefficient, Kco, also known as the transfer factor per unit alveolar volume, [Tl/Va]), is one of the most useful clinical tests of pulmonary function, the only one which specifically focuses on pulmonary microcirculation. It was originally devised in 1909 as a physiological tool to assess the diffusive capacity of the lung as a gas exchanger. It was subsequently developed as a clinical tool, but cumbersome analytical techniques delayed its introduction into clinical medicine until 1950s. The physiology of the carbon monoxide transfer factor (also called the diffusing capacity Dl,co) is based on the Roughton-Forster equation which partitions Dl,co, a conductance, into membrane (Dm) and red cell (thetaVc) diffusion conductances. Recent work (1987-2001) suggests that 70-80% of the resistance to CO (and O2) diffusion may reside in the red cell fraction. The clinical implication is that Tl,co and Kco are 'windows' onto the pulmonary microcirculation. As regards reference values for clinical use, Tl,co depends on age, height and gender. Kco, which is actually a rate constant, is independent of gender, and is affected principally by age. A schema is presented for the clinical interpretation of Tl,co. As Tl,co is derived from the product of Kco and the accessible alveolar volume (Va), examination of these two components (Kco and Va) will usually suggest a specific pathophysiological mechanism as the explanation for a reduction in Tl,co.
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