Measurement of CO diffusion capacity (II): Standardisation and quality criteria

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Salcedo-Posadas, J.R. Villa-Asensi, I. de Mir Messa, O. Sardon-Prado, H. Larramona" "autores" => array:5 [ 0 => array:3 [ "nombre" => "A." "apellidos" => "Salcedo-Posadas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "J.R." "apellidos" => "Villa-Asensi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "I." "apellidos" => "de Mir Messa" "email" => array:2 [ 0 => "idemir@vhebron.net" 1 => "fernandezdemir@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 3 => array:3 [ "nombre" => "O." "apellidos" => "Sardon-Prado" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 4 => array:3 [ "nombre" => "H." "apellidos" => "Larramona" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Sección de Neumología, Hospital Maternoinfantil Gregorio Marañón, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Sección de Neumología, Hospital Infantil Universitario Niño Jesús, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Sección de Neumología Pediátrica y Fibrosis Quística, Hospital Universitario Vall d¿Hebron, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Sección de Neumología Pediátrica, Hospital Universitario Donostia, San Sebastián, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Pediatría, Facultad de Medicina y Odontología, UPV/EHU, San Sebastián, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Sección de Neumología Pediátrica, Consorci Hospitalari Parc Taulí, Sabadell, Barcelona, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Medición de la difusión de CO (II): estandarización y criterios de calidad" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 829 "Ancho" => 1613 "Tamanyo" => 85117 ] ] "descripcion" => array:1 [ "en" => "Structure of the gas exchange barrier." ] ] ] "textoCompleto" => "IntroductionThe main function of the lungs is to establish the exchange of oxygen (O2) and carbon dioxide (CO2) between tissue and ambient air. Gas exchange depends on three processes: ventilation, diffusion and pulmonary perfusion.The diffusion process is defined as the flow of particles from an area of greater concentration to an area of lesser concentration. The rate of transfer by diffusion of any gas through a membrane (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) is directly proportional to the surface area of the membrane and inversely proportional to its thickness; it also depends on the molecular weight, pressure gradient and solubility of the gas, the ventilation-perfusion ratio of the lung units, the rate of combination with haemoglobin and the haemoglobin values. The diffusion rate of CO2 is 20 times higher than that of O2.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Measuring diffusion provides information on gas transfer between the alveoli and the blood of the pulmonary capillaries and we generally refer to it as diffusion capacity (DLCO).<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> To assess the functional integrity of the diffusion process a gas must be used that is not present in venous blood, that has an affinity for haemoglobin and that is soluble in blood. The gas universally used is carbon monoxide (CO).CO diffusing capacity (DLCO) is the uptake of this gas per minute (VCO: mL of CO transferred per minute) in relation to the CO gradient through alveolar-capillary membrane (the difference between the partial pressures of CO in the alveoli [PACO] and in the capillary blood [PCCO] in mmHg).<elsevierMultimedia ident="eq0005"></elsevierMultimedia>There are currently new methods for measuring diffusion capacity using nitric oxide (NO), as this gas is independent of O2 pressure and haematocrit and has a greater affinity for haemoglobin (Hb) than CO. Moreover, DLNO is less influenced by capillary blood volume than DLCO and represents the true diffusing capacity of the alveolar-capillary membrane. In addition, the DLNO/DLCO ratio could be a good indicator of impairment in gas exchange, which would be an improvement on the tests currently used in clinical practice.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> In cystic fibrosis, combined analysis with CO and NO could improve its functional assessment.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Research is also being conducted on the influence of breath-hold time on diffusion capacity of NO compared with CO.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> The use of NO is therefore a promising method.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>Techniques for measuring diffusionThere are three main methods for measuring DLCO: (a) the rebreathing technique, (b) the multiple-breath or steady state technique, and (c) the single-breath (SB) technique. The most widely used and best standardised method is the last of these.<a class="elsevierStyleCrossRef" href="#bib0040">8</a><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">(a)Rebreathing method: the patient breathes for 10–15s into a small bag containing CO and helium (He). Little used in clinical practice.</li><li class="elsevierStyleListItem" id="lsti0010">(b)Multiple-breath technique: many children have difficulties in holding their breath for 10s or have a vital capacity (VC) lower than 1.5L, so that they cannot perform the single-breath technique; other techniques have therefore been devised.<a class="elsevierStyleCrossRef" href="#bib0045">9</a></li></ul>The most commonly used is called the multiple-breath or steady state technique, in which the patient is told to take normal breaths at tidal volume after being connected to a closed system filled with a gas mixture containing 5% He and 0.3% CO, so that the disappearance of CO from the system and the fall in He due to dilution are continuously monitored. During the procedure CO2 is absorbed, while O2 is kept between 20% and 22%. The ventilation of the child is measured with a displacement transducer connected to the bellows or piston, which moves as the patient breathes while the He, CO and O2 concentrations are continuously monitored. As the patient is connected to the system at functional residual capacity (FRC) level, this FRC is determined by He dilution, whereas diffusing capacity is calculated from the exponential decay in CO. The results depend on alveolar ventilation, and the breathing pattern must be as stable as possible.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>An inhalation bag with a two-way valve, containing a mixture of CO at a certain concentration, can also be used. The patient breathes several times and the exhaled gas is collected and analysed. The CO uptake is obtained by multiplying the difference between the inhaled and exhaled concentrations by the ventilation volume per minute. The partial alveolar pressure of CO at which the transfer is made also needs to be measured.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>There are predicted values for DLCO and DLCO/VA with this technique for patients aged from 6 to 18.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>It is to be expected that the use of new systems, which analyse CO breath by breath, not estimating its concentration but determining it in real time, may avoid errors that arise with the other techniques.Nevertheless, new validation and standardisation studies of this technique are needed.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">(c)Single-breath method (DLCOSB): measuring DLCO per single breath involves making the patient exhale to residual volume (RV) and then take in a rapid breath of a gas containing CO 0.3%, He 10%, O2 21% and nitrogen in equilibrium, to over 90% of vital capacity. After rapid inhalation of the gas, the breath is held for 10s at total lung capacity (TLC) to allow it to diffuse and then the patient is made to exhale rapidly. The first part (between 0.5 and 1L) is discarded, as it corresponds to the dead space that has not undergone the diffusion process, and the second, representing the gas that has been in the alveoli (alveolar fraction), is used. In this second fraction the final concentration of CO and He is determined. The initial concentration of CO in the alveolar gas is not the same as the concentration of CO in the inhaled gas administered to the patient, since this gas has to be diluted in the air present in the lung after maximum exhalation (RV) and air in the dead space in the system. Since only the concentration of the gas administered is known and not that present in the alveolar space, a tracer gas (generally He) is used to calculate the latter. He is an inert gas, which is not diffused through the alveolar-capillary membrane. Therefore, if we know the initial concentration of He in the gas administered (HeI) and the volume of gas inhaled (measured with the spirometer), the final concentration of helium (HeE), measured in the exhaled air, will depend on the final volume in which the He has been dissolved (alveolar volume+dead space).</li></ul><elsevierMultimedia ident="eq0010"></elsevierMultimedia>Knowing this final volume we can easily calculate the initial alveolar CO concentration FACOi:<elsevierMultimedia ident="eq0015"></elsevierMultimedia>Using He also enables us to calculate the alveolar volume (VA), which will be the volume of air in the alveolar space (that which is diffused).<elsevierMultimedia ident="eq0020"></elsevierMultimedia>The dead space depends both on the dead space in the system (it must be less than 100mL), which we know, and on the anatomical dead space (2.2mL/kg of body weight).The main criticism of this method is that it measures diffusion in a very unphysiological situation: during a maximum inhalation and while the breath is held, which does not occur in normal breathing at tidal volume.Another of the problems with DLCO is that we are using a single value to express the diverse properties of millions of respiratory units, which differ according to the region of the lung.Single-breath DLCO depends on the amount of lung tissue involved in the gas exchange. For this reason it is advisable in these patients to assess diffusing capacity per unit of lung volume, KCO (DLCO/VA).<a class="elsevierStyleCrossRefs" href="#bib0065">13,14</a>The complexity of the technique, the reference equations for the test, differences in equipment, interpatient variability and the conditions in which the test is performed mean that there is a high degree of interlaboratory variability,<a class="elsevierStyleCrossRef" href="#bib0075">15</a> much greater than with other pulmonary function measurements, and standardisation is therefore essential.<a class="elsevierStyleCrossRefs" href="#bib0010">2,8,16,17</a> Reference values have been established in healthy white children aged from 5 to 19 for DLCO and VA.<a class="elsevierStyleCrossRef" href="#bib0090">18</a>We must not forget that the absolute values obtained with these two techniques, single- and multiple-breath, are different, as they are performed at total lung capacity (TLC) and functional residual capacity (FRC) respectively, and diffusion capacity is related to the surface area assessed, which is lower in the latter; therefore when the two techniques are compared the results have to be calculated as z-scores or standard deviations from the corresponding predicted values.Practical aspects of the techniquePreparation of the patientThe patient must refrain from smoking for 24h before the test, avoid alcohol for at least 4h and not take exercise. He or she will remain seated for at least 5min before the test and throughout the procedure.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>If the patient requires oxygen it is preferable to discontinue it at least 5min before beginning the test. If this is not possible, the results must be assessed with caution.EquipmentThe patient breathes through a pneumotacograph, which measures the volume of air inhaled and is connected to a three-way valve, which initially allows the patient to breathe ambient air; subsequently, during forced inhalation, the way is opened to the gas cylinder, and during exhalation it is opened to the bag in which the alveolar gas sample is collected. During the 10s for which the breath is held there must be a shutter that prevents exhalation and also a pressure sensor to assess whether the patient is performing Valsalva manoeuvres (exhalation) or Müller's manoeuvres (inhalation), which modify pulmonary capillary blood volume. The Valsalva manoeuvre reduces DLCO and Müller's manoeuvre increases it.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Finally, gas analysers are needed to ascertain the concentration of exhaled CO and He. The system must have a dead space of less than 100mL. All the apparatuses must be calibrated daily.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>Test procedure<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020">1)Explain the manoeuvre. It is advisable to carry out a simulation first without gas inhalation.</li><li class="elsevierStyleListItem" id="lsti0025">2)The mouthpiece is placed in the mouth and the clip on the nose and the patient is asked to breathe calmly.</li><li class="elsevierStyleListItem" id="lsti0030">3)The patient is told to exhale to RV. If there is a major obstructive disease it is recommended that exhalation should be limited to 6s.</li><li class="elsevierStyleListItem" id="lsti0035">4)A rapid breath is taken to TLC:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0040">a)The inspiratory volume (IV) must be at least 90% of the largest previous VC (spirometry must be performed beforehand as a guide).</li><li class="elsevierStyleListItem" id="lsti0045">b)The inspiration must be rapid enough for 90% of the IV to be inhaled within 1.5–2s in healthy individuals and in less than 4s in patients with obstructive disease. If the inhalation lasts for 5s, DLCO increases by around 13%.</li></ul></li><li class="elsevierStyleListItem" id="lsti0050">5)The breath must be held for 10s.<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0055">a)During this time no expiratory or inspiratory effort must be made against the shutter.</li></ul></li><li class="elsevierStyleListItem" id="lsti0060">6)After this the patient must exhale rapidly.<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0065">a)The first part (about 750mL) is discarded. If the patient has a VC<2L this can be reduced to 500mL.</li><li class="elsevierStyleListItem" id="lsti0070">b)The volume analysed must be between 500 and 1000mL and must be exhaled in less than 4s.</li></ul></li><li class="elsevierStyleListItem" id="lsti0075">7)The patient is told to remove the nose clip and remain seated.</li><li class="elsevierStyleListItem" id="lsti0080">8)The test must be repeated until at least two values are achieved that agree within 10% and below 3mL/min/mmHg. At least 4min must elapse between each test. In patients with major obstruction it may be necessary to wait up to 10min between tests for the gases to be completely eliminated. It may be useful to ask the patient to take deep breaths so as to eliminate the gas more effectively.</li><li class="elsevierStyleListItem" id="lsti0085">9)Calculations:</li></ul><elsevierMultimedia ident="eq0025"></elsevierMultimedia>VASTPD=alveolar volume at STPD; 60/t=breath-hold time converted into minutes; PB–47=barometric pressure minus water vapour pressure at 37°C; ln=natural logarithm; FACOo=alveolar CO concentration at the start of diffusion; FACOt=alveolar CO concentration at the end of the test.<elsevierMultimedia ident="eq0030"></elsevierMultimedia>HeE=exhaled He concentration; HeI=inhaled He concentration; COI=inhaled CO concentration; COE=exhaled CO concentration.Given that diffusing capacity is calculated per unit of time (mL of CO absorbed per minute), exact calculation of the time the patient holds his or her breath, which is the time during which CO diffusion takes place, is crucial.<a class="elsevierStyleCrossRefs" href="#bib0110">22,23</a> The Jones–Meade method for measuring the time starts counting from 30% of the inhalation time and stops at 50% of the alveolar gas sample collection time (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>In patients with obstruction it may be preferable to perform the test after using a bronchodilator, although if heart rate increases, volume per minute also increases, raising DLCO. For this reason it is advisable to carry out the test at least 30min after administering the bronchodilator.AdjustmentsAdjustment for haemoglobin (Hb)Patients with anaemia have a reduced DLCO because CO uptake by erythrocytes is lower. The Cotes method<a class="elsevierStyleCrossRef" href="#bib0120">24</a> of correction for Hb makes it possible to calculate adjusted DLCO in adult males with Hb greater than 14.6g/dL or in women and in children under 15 with Hb<13.4g/dL.Males 15 years of age and older:<elsevierMultimedia ident="eq0035"></elsevierMultimedia>Children aged <15 years and women:<elsevierMultimedia ident="eq0040"></elsevierMultimedia>It is advisable to put both values in the report: the measured DLCO and the DLCO adjusted for Hb.Clinical applicationsCO transfer can be either increased or reduced in various processes (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0040">8</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>CO transfer is increased in situations in which there is an increase in blood volume in the pulmonary capillaries (exercise, left-right shunts), polycythaemia and pulmonary haemorrhage (falsely elevated DLCO). Occasionally there is a rise in DLCO in asthmatics, due to an increase in pulmonary blood volume though negative intrathoracic pressure produced after rapid inhalations.DLCO is decreased in patients with a reduction in alveolar volume or in diffusion defects (alteration of the alveolar-capillary membrane [interstitial lung disease: idiopathic pulmonary fibrosis, extrinsic allergic alveolitis, scleroderma, sarcoidosis, asbestosis] or decreased pulmonary capillary blood volume [pulmonary embolism or primary pulmonary hypertension]). In pulmonary emphysema DLCO is characteristically reduced by loss of alveolar-capillary membrane surface area secondary to alveolar rupture, giving rise to an increase in TLC with a decreased KCO (DLCO/VA). In congestive heart failure the reduction in DLCO may be secondary to interstitial oedema. Other causes of decreased DLCO are anaemia, renal failure, smoking and marijuana use.In patients with restrictive diseases, especially in children with deformities of the rib cage or neuromuscular diseases in which normal lungs are restrictive because of deformity or muscular weakness, the surface area for diffusion is relatively large per unit of pulmonary volume, and for this reason DLCO may be normal. The patient's DLCO/VA should therefore be compared with reference values based on his or her (restrictive) TLC rather than his or her theoretical TLC.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>In cystic fibrosis both raising and lowering of DLCO may be found. Initially the transfer factor may be elevated by an increase in the amount of blood reaching the lung, due to fluctuations in pleural pressure secondary to bronchial obstruction; later, with the onset of pulmonary heart disease, pulmonary microcirculation is impaired and diffusion is gradually reduced.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>Indications for the DLCO test are set out in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<a class="elsevierStyleCrossRef" href="#bib0105">21</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>In practice the main indications in paediatrics are as follows<a class="elsevierStyleCrossRef" href="#bib0050">10</a>:Monitoring of treatments that are toxic to the lungsChemotherapy (methotrexate, nitrofurantoin, azathioprine, penicillamine, cyclophosphamide and especially bleomycin) can produce a major decrease in DLCO, which must be monitored.Chest radiation can cause irreversible diffusion impairment.Treatments for autoimmune or rheumatological diseases can also impair pulmonary diffusion.Immunosuppressants used after organ transplants have been associated with obstructive and restrictive lung disease.Diagnosis and monitoring of patients with chronic interstitial lung diseaseImpairment of diffusing capacity is one of the initial signs of interstitial lung disease and a fundamental indicator of clinical course and response to treatment.Monitoring of children with diseases that cause pulmonary bleedingIn primary pulmonary haemosiderosis, Goodpasture syndrome and granulomatosis with polyangiitis, an increase in diffusing capacity can predict relapse or indicate progression in asymptomatic patients. Moreover, pulmonary haemosiderosis that does not respond to treatment may eventually give rise to pulmonary fibrosis, leading to decreased diffusion." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres541350" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec560883" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres541349" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec560882" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Techniques for measuring diffusion" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Practical aspects of the technique" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Preparation of the patient" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Equipment" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Test procedure" ] ] ] 7 => array:3 [ "identificador" => "sec0035" "titulo" => "Adjustments" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Adjustment for haemoglobin (Hb)" ] ] ] 8 => array:3 [ "identificador" => "sec0045" "titulo" => "Clinical applications" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Monitoring of treatments that are toxic to the lungs" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Diagnosis and monitoring of patients with chronic interstitial lung disease" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Monitoring of children with diseases that cause pulmonary bleeding" ] ] ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-09-29" "fechaAceptado" => "2014-10-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec560883" "palabras" => array:3 [ 0 => "Lung diffusion capacity" 1 => "Single breath technique" 2 => "Practical aspects" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec560882" "palabras" => array:3 [ 0 => "Capacidad de difusión" 1 => "Técnica de la respiración única" 2 => "Aplicaciones clínicas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The diffusion capacity is the technique that measures the ability of the respiratory system for gas exchange, thus allowing a diagnosis of the malfunction of the alveolar-capillary unit. The most important parameter to assess is the CO diffusion capacity (DLCO). New methods are currently being used to measure the diffusion using nitric oxide (NO). There are other methods for measuring diffusion, although in this article the single breath technique is mainly referred to, as it is the most widely used and best standardised.Its complexity, its reference equations, differences in equipment, inter-patient variability and conditions in which the DLCO is performed, lead to a wide inter-laboratory variability, although its standardisation makes this a more reliable and reproductive method.The practical aspects of the technique are analysed, by specifying the recommendations to carry out a suitable procedure, the calibration routine, calculations and adjustments. Clinical applications are also discussed. An increase in the transfer of CO occurs in diseases in which there is an increased volume of blood in the pulmonary capillaries, such as in polycythemia and pulmonary haemorrhage. There is a decrease in DLCO in patients with alveolar volume reduction or diffusion defects, either by altered alveolar-capillary membrane (interstitial diseases) or decreased volume of blood in the pulmonary capillaries (pulmonary embolism or primary pulmonary hypertension). Other causes of decreased or increased DLCO are also highlighted." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La capacidad de difusión es la técnica que mide la capacidad del aparato respiratorio para realizar el intercambio gaseoso y así diagnosticar la disfunción de la unidad alvéolo-capilar.El parámetro más importante a evaluar es la capacidad de difusión del CO (DLCO). Actualmente hay nuevos métodos para medir la capacidad de difusión utilizando óxido nítrico (NO). Existen diferentes métodos de medida, aunque en este artículo nos referiremos sobre todo a la técnica de la respiración única, la más utilizada y mejor estandarizada.Su complejidad, sus ecuaciones de referencia, las diferencias en equipamiento, la variabilidad interpacientes y las condiciones en las que se realiza hacen que exista una gran variabilidad interlaboratorio, habiéndose realizado estandarizaciones para hacer este método más fiable y reproducible.Se analizan los aspectos prácticos de la técnica, especificando las recomendaciones para la realización de un procedimiento adecuado, sistemática de calibración y cálculos y ajustes necesarios. También se exponen sus aplicaciones clínicas.Se produce un aumento de la transferencia de CO en las enfermedades en las que existe un aumento del volumen sanguíneo en los capilares pulmonares, en la policitemia y en la hemorragia pulmonar. Existe una disminución de la DLCO en los pacientes con reducción del volumen alveolar o en los defectos de difusión, ya sea por alteración de la membrana alvéolo-capilar (enfermedad intersticial) o por disminución del volumen de sangre en los capilares pulmonares (embolia pulmonar o hipertensión pulmonar primaria). También se exponen otras causas de disminución o aumento de la DLCO." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Posadas AS, Asensi JRV, de MirMessa I, Prado OS, Larramona H. Medición de la difusión de CO (II): estandarización y criterios de calidad. An Pediatr (Barc). 2015;83:137.e1–137.e7." ] ] "multimedia" => array:12 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 829 "Ancho" => 1613 "Tamanyo" => 85117 ] ] "descripcion" => array:1 [ "en" => "Structure of the gas exchange barrier." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 945 "Ancho" => 1615 "Tamanyo" => 80406 ] ] "descripcion" => array:1 [ "en" => "Graphic illustration of the Ogilvie and Jones–Meade methods for calculating breath-hold time during the DLCO manoeuvre." ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Extrapulmonary reduction in alveolar volume \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Reduced respiratory effort or muscular debility \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Thoracic deformities preventing full inflation of the thorax \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Situations involving reduction of the CO-Hb reaction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anaemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pulmonary embolism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Changes in haemoglobin's binding properties (carboxyhaemoglobin, increased FiO2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Conditions that alter the alveolar-capillary membrane and the CO-Hb binding, reducing DLCO \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pulmonary resection (there may be a compensating increase in the CO-Hb reaction) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Emphysema \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Interstitial lung disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pulmonary oedema \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pulmonary vasculitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pulmonary hypertension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Situations that increase the CO-Hb reaction and raise DLCO \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Polycythaemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Left-right shunt \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pulmonary haemorrhage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Asthma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Changes in the Hb binding properties (reduced FiO2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Müller's manoeuvre (reduction in intrathoracic pressure) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Exercise \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Supine position \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Obesity \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab869328.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Processes associated with alterations in DLCO." ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1. Evaluation and followup of diseases affecting lung parenchyma (those associated with drug reactions, pneumoconiosis or sarcoidosis) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2. Evaluation and followup of emphysema \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3. Differentiating between chronic bronchitis, emphysema and asthma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4. Assessment of pulmonary involvement in systemic diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5. Assessment of cardiovascular diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">6. Prediction of arterial desaturation during exercise in some patients with lung disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">7. Assessment and quantification of the degree of disability associated with pulmonary fibrosis or with emphysema \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">8. Assessment of the pulmonary effects of chemotherapy agents or other drugs that induce pulmonary dysfunction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">9. Assessment of pulmonary haemorrhage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">10. As an early indicator of certain pulmonary infections that cause diffuse pneumonitis (e.g., Pneumocystis pneumonia) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab869329.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Indications for DLCO measurement." ] ] 4 => array:5 [ "identificador" => "eq0005" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "DLCOVCOPACO−PCCOmL/min/mmHg" "Fichero" => "STRIPIN_si1.jpeg" "Tamanyo" => 2613 "Alto" => 32 "Ancho" => 225 ] ] 5 => array:5 [ "identificador" => "eq0010" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "Volume   inhaled×[HeI]=Final   volume×[HeE]" "Fichero" => "STRIPIN_si2.jpeg" "Tamanyo" => 2865 "Alto" => 14 "Ancho" => 321 ] ] 6 => array:5 [ "identificador" => "eq0015" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "FACOi=Volume   inhaled×[CO   inhaled]/Final   volume" "Fichero" => "STRIPIN_si3.jpeg" "Tamanyo" => 3254 "Alto" => 14 "Ancho" => 369 ] ] 7 => array:5 [ "identificador" => "eq0020" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "VA=(volume   inhaled−dead   space)×[HeI]/[HeE]" "Fichero" => "STRIPIN_si4.jpeg" "Tamanyo" => 3023 "Alto" => 14 "Ancho" => 343 ] ] 8 => array:5 [ "identificador" => "eq0025" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "DLCO=VASTPD×60t×1PB–47×lnFACOoFACOt" "Fichero" => "STRIPIN_si5.jpeg" "Tamanyo" => 3045 "Alto" => 33 "Ancho" => 271 ] ] 9 => array:5 [ "identificador" => "eq0030" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "FACOoFACOt=HeEHeI×COICOE" "Fichero" => "STRIPIN_si6.jpeg" "Tamanyo" => 2101 "Alto" => 33 "Ancho" => 136 ] ] 10 => array:5 [ "identificador" => "eq0035" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "DLCO   adjusted   for   Hb=measured   DLCO×(10.22+Hb)/(1.7×Hb)" "Fichero" => "STRIPIN_si7.jpeg" "Tamanyo" => 4130 "Alto" => 42 "Ancho" => 293 ] ] 11 => array:5 [ "identificador" => "eq0040" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "DLCO   adjusted   for   Hb=measured   DLCO×(9.38+Hb)/(1.7×Hb)" "Fichero" => "STRIPIN_si8.jpeg" "Tamanyo" => 4079 "Alto" => 42 "Ancho" => 293 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Single-breath carbon monoxide diffusing capacity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. 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Measurement of CO diffusion capacity (II): Standardisation and quality criteria

Medición de la difusión de CO (II): estandarización y criterios de calidad

A. Salcedo-Posadasa, J.R. Villa-Asensib, I. de Mir Messac,

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idemir@vhebron.net
fernandezdemir@gmail.com

Corresponding author.

, O. Sardon-Pradod,e, H. Larramonaf

a Sección de Neumología, Hospital Maternoinfantil Gregorio Marañón, Madrid, Spain

b Sección de Neumología, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

c Sección de Neumología Pediátrica y Fibrosis Quística, Hospital Universitario Vall d¿Hebron, Barcelona, Spain

d Sección de Neumología Pediátrica, Hospital Universitario Donostia, San Sebastián, Spain

e Departamento de Pediatría, Facultad de Medicina y Odontología, UPV/EHU, San Sebastián, Spain

f Sección de Neumología Pediátrica, Consorci Hospitalari Parc Taulí, Sabadell, Barcelona, Spain

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it also depends on the molecular weight&#44; pressure gradient and solubility of the gas&#44; the ventilation-perfusion ratio of the lung units&#44; the rate of combination with haemoglobin and the haemoglobin values&#46; The diffusion rate of CO<span class="elsevierStyleInf">2</span> is 20 times higher than that of O<span class="elsevierStyleInf">2</span>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Measuring diffusion provides information on gas transfer between the alveoli and the blood of the pulmonary capillaries and we generally refer to it as diffusion capacity &#40;DLCO&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> To assess the functional integrity of the diffusion process a gas must be used that is not present in venous blood&#44; that has an affinity for haemoglobin and that is soluble in blood&#46; The gas universally used is carbon monoxide &#40;CO&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">CO diffusing capacity &#40;DLCO&#41; is the uptake of this gas per minute &#40;VCO&#58; mL of CO transferred per minute&#41; in relation to the CO gradient through alveolar-capillary membrane &#40;the difference between the partial pressures of CO in the alveoli &#91;PACO&#93; and in the capillary blood &#91;PCCO&#93; in mmHg&#41;&#46;<elsevierMultimedia ident="eq0005"></elsevierMultimedia></p><p id="par0025" class="elsevierStylePara elsevierViewall">There are currently new methods for measuring diffusion capacity using nitric oxide &#40;NO&#41;&#44; as this gas is independent of O<span class="elsevierStyleInf">2</span> pressure and haematocrit and has a greater affinity for haemoglobin &#40;Hb&#41; than CO&#46; Moreover&#44; DLNO is less influenced by capillary blood volume than DLCO and represents the true diffusing capacity of the alveolar-capillary membrane&#46; In addition&#44; the DLNO&#47;DLCO ratio could be a good indicator of impairment in gas exchange&#44; which would be an improvement on the tests currently used in clinical practice&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> In cystic fibrosis&#44; combined analysis with CO and NO could improve its functional assessment&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Research is also being conducted on the influence of breath-hold time on diffusion capacity of NO compared with CO&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The use of NO is therefore a promising method&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Techniques for measuring diffusion</span><p id="par0030" class="elsevierStylePara elsevierViewall">There are three main methods for measuring DLCO&#58; &#40;a&#41; the <span class="elsevierStyleItalic">rebreathing</span> technique&#44; &#40;b&#41; the multiple-breath or <span class="elsevierStyleItalic">steady state</span> technique&#44; and &#40;c&#41; the <span class="elsevierStyleItalic">single-breath</span> &#40;SB&#41; technique&#46; The most widely used and best standardised method is the last of these&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#40;a&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Rebreathing method</span>&#58; the patient breathes for 10&#8211;15<span class="elsevierStyleHsp" style=""></span>s into a small bag containing CO and helium &#40;He&#41;&#46; Little used in clinical practice&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#40;b&#41;</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Multiple-breath technique</span>&#58; many children have difficulties in holding their breath for 10<span class="elsevierStyleHsp" style=""></span>s or have a vital capacity &#40;VC&#41; lower than 1&#46;5<span class="elsevierStyleHsp" style=""></span>L&#44; so that they cannot perform the single-breath technique&#59; other techniques have therefore been devised&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">The most commonly used is called the multiple-breath or steady state technique&#44; in which the patient is told to take normal breaths at tidal volume after being connected to a closed system filled with a gas mixture containing 5&#37; He and 0&#46;3&#37; CO&#44; so that the disappearance of CO from the system and the fall in He due to dilution are continuously monitored&#46; During the procedure CO<span class="elsevierStyleInf">2</span> is absorbed&#44; while O<span class="elsevierStyleInf">2</span> is kept between 20&#37; and 22&#37;&#46; The ventilation of the child is measured with a displacement transducer connected to the bellows or piston&#44; which moves as the patient breathes while the He&#44; CO and O<span class="elsevierStyleInf">2</span> concentrations are continuously monitored&#46; As the patient is connected to the system at functional residual capacity &#40;FRC&#41; level&#44; this FRC is determined by He dilution&#44; whereas diffusing capacity is calculated from the exponential decay in CO&#46; The results depend on alveolar ventilation&#44; and the breathing pattern must be as stable as possible&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">An inhalation bag with a two-way valve&#44; containing a mixture of CO at a certain concentration&#44; can also be used&#46; The patient breathes several times and the exhaled gas is collected and analysed&#46; The CO uptake is obtained by multiplying the difference between the inhaled and exhaled concentrations by the ventilation volume per minute&#46; The partial alveolar pressure of CO at which the transfer is made also needs to be measured&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">There are predicted values for DLCO and DLCO&#47;VA with this technique for patients aged from 6 to 18&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">It is to be expected that the use of new systems&#44; which analyse CO breath by breath&#44; not estimating its concentration but determining it in real time&#44; may avoid errors that arise with the other techniques&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Nevertheless&#44; new validation and standardisation studies of this technique are needed&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#40;c&#41;</span><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Single-breath method</span> &#40;DLCOSB&#41;&#58; measuring DLCO per single breath involves making the patient exhale to residual volume &#40;RV&#41; and then take in a rapid breath of a gas containing CO 0&#46;3&#37;&#44; He 10&#37;&#44; O<span class="elsevierStyleInf">2</span> 21&#37; and nitrogen in equilibrium&#44; to over 90&#37; of vital capacity&#46; After rapid inhalation of the gas&#44; the breath is held for 10<span class="elsevierStyleHsp" style=""></span>s at total lung capacity &#40;TLC&#41; to allow it to diffuse and then the patient is made to exhale rapidly&#46; The first part &#40;between 0&#46;5 and 1<span class="elsevierStyleHsp" style=""></span>L&#41; is discarded&#44; as it corresponds to the dead space that has not undergone the diffusion process&#44; and the second&#44; representing the gas that has been in the alveoli &#40;alveolar fraction&#41;&#44; is used&#46; In this second fraction the final concentration of CO and He is determined&#46; The initial concentration of CO in the alveolar gas is not the same as the concentration of CO in the inhaled gas administered to the patient&#44; since this gas has to be diluted in the air present in the lung after maximum exhalation &#40;RV&#41; and air in the dead space in the system&#46; Since only the concentration of the gas administered is known and not that present in the alveolar space&#44; a tracer gas &#40;generally He&#41; is used to calculate the latter&#46; He is an inert gas&#44; which is not diffused through the alveolar-capillary membrane&#46; Therefore&#44; if we know the initial concentration of He in the gas administered &#40;He<span class="elsevierStyleInf"><span class="elsevierStyleItalic">I</span></span>&#41; and the volume of gas inhaled &#40;measured with the spirometer&#41;&#44; the final concentration of helium &#40;He<span class="elsevierStyleInf"><span class="elsevierStyleItalic">E</span></span>&#41;&#44; measured in the exhaled air&#44; will depend on the final volume in which the He has been dissolved &#40;alveolar volume<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>dead space&#41;&#46;</p></li></ul><elsevierMultimedia ident="eq0010"></elsevierMultimedia>Knowing this final volume we can easily calculate the initial alveolar CO concentration FACO<span class="elsevierStyleInf"><span class="elsevierStyleItalic">i</span></span>&#58;<elsevierMultimedia ident="eq0015"></elsevierMultimedia>Using He also enables us to calculate the alveolar volume &#40;VA&#41;&#44; which will be the volume of air in the alveolar space &#40;that which is diffused&#41;&#46;<elsevierMultimedia ident="eq0020"></elsevierMultimedia>The dead space depends both on the dead space in the system &#40;it must be less than 100<span class="elsevierStyleHsp" style=""></span>mL&#41;&#44; which we know&#44; and on the anatomical dead space &#40;2&#46;2<span class="elsevierStyleHsp" style=""></span>mL&#47;kg of body weight&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The main criticism of this method is that it measures diffusion in a very unphysiological situation&#58; during a maximum inhalation and while the breath is held&#44; which does not occur in normal breathing at tidal volume&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Another of the problems with DLCO is that we are using a single value to express the diverse properties of millions of respiratory units&#44; which differ according to the region of the lung&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Single-breath DLCO depends on the amount of lung tissue involved in the gas exchange&#46; For this reason it is advisable in these patients to assess diffusing capacity per unit of lung volume&#44; KCO &#40;DLCO&#47;VA&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The complexity of the technique&#44; the reference equations for the test&#44; differences in equipment&#44; interpatient variability and the conditions in which the test is performed mean that there is a high degree of interlaboratory variability&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> much greater than with other pulmonary function measurements&#44; and standardisation is therefore essential&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;8&#44;16&#44;17</span></a> Reference values have been established in healthy white children aged from 5 to 19 for DLCO and VA&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">We must not forget that the absolute values obtained with these two techniques&#44; single- and multiple-breath&#44; are different&#44; as they are performed at total lung capacity &#40;TLC&#41; and functional residual capacity &#40;FRC&#41; respectively&#44; and diffusion capacity is related to the surface area assessed&#44; which is lower in the latter&#59; therefore when the two techniques are compared the results have to be calculated as z-scores or standard deviations from the corresponding predicted values&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Practical aspects of the technique</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Preparation of the patient</span><p id="par0100" class="elsevierStylePara elsevierViewall">The patient must refrain from smoking for 24<span class="elsevierStyleHsp" style=""></span>h before the test&#44; avoid alcohol for at least 4<span class="elsevierStyleHsp" style=""></span>h and not take exercise&#46; He or she will remain seated for at least 5<span class="elsevierStyleHsp" style=""></span>min before the test and throughout the procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">If the patient requires oxygen it is preferable to discontinue it at least 5<span class="elsevierStyleHsp" style=""></span>min before beginning the test&#46; If this is not possible&#44; the results must be assessed with caution&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Equipment</span><p id="par0110" class="elsevierStylePara elsevierViewall">The patient breathes through a pneumotacograph&#44; which measures the volume of air inhaled and is connected to a three-way valve&#44; which initially allows the patient to breathe ambient air&#59; subsequently&#44; during forced inhalation&#44; the way is opened to the gas cylinder&#44; and during exhalation it is opened to the bag in which the alveolar gas sample is collected&#46; During the 10<span class="elsevierStyleHsp" style=""></span>s for which the breath is held there must be a shutter that prevents exhalation and also a pressure sensor to assess whether the patient is performing Valsalva manoeuvres &#40;exhalation&#41; or M&#252;ller&#39;s manoeuvres &#40;inhalation&#41;&#44; which modify pulmonary capillary blood volume&#46; The Valsalva manoeuvre reduces DLCO and M&#252;ller&#39;s manoeuvre increases it&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Finally&#44; gas analysers are needed to ascertain the concentration of exhaled CO and He&#46; The system must have a dead space of less than 100<span class="elsevierStyleHsp" style=""></span>mL&#46; All the apparatuses must be calibrated daily&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Test procedure</span><p id="par0115" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">1&#41;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Explain the manoeuvre&#46; It is advisable to carry out a simulation first without gas inhalation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">2&#41;</span><p id="par0125" class="elsevierStylePara elsevierViewall">The mouthpiece is placed in the mouth and the clip on the nose and the patient is asked to breathe calmly&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">3&#41;</span><p id="par0130" class="elsevierStylePara elsevierViewall">The patient is told to exhale to RV&#46; If there is a major obstructive disease it is recommended that exhalation should be limited to 6<span class="elsevierStyleHsp" style=""></span>s&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">4&#41;</span><p id="par0135" class="elsevierStylePara elsevierViewall">A rapid breath is taken to TLC&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">a&#41;</span><p id="par0140" class="elsevierStylePara elsevierViewall">The inspiratory volume &#40;IV&#41; must be at least 90&#37; of the largest previous VC &#40;spirometry must be performed beforehand as a guide&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">b&#41;</span><p id="par0145" class="elsevierStylePara elsevierViewall">The inspiration must be rapid enough for 90&#37; of the IV to be inhaled within 1&#46;5&#8211;2<span class="elsevierStyleHsp" style=""></span>s in healthy individuals and in less than 4<span class="elsevierStyleHsp" style=""></span>s in patients with obstructive disease&#46; If the inhalation lasts for 5<span class="elsevierStyleHsp" style=""></span>s&#44; DLCO increases by around 13&#37;&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">5&#41;</span><p id="par0150" class="elsevierStylePara elsevierViewall">The breath must be held for 10<span class="elsevierStyleHsp" style=""></span>s&#46;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">a&#41;</span><p id="par0155" class="elsevierStylePara elsevierViewall">During this time no expiratory or inspiratory effort must be made against the shutter&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">6&#41;</span><p id="par0160" class="elsevierStylePara elsevierViewall">After this the patient must exhale rapidly&#46;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">a&#41;</span><p id="par0165" class="elsevierStylePara elsevierViewall">The first part &#40;about 750<span class="elsevierStyleHsp" style=""></span>mL&#41; is discarded&#46; If the patient has a VC<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>L this can be reduced to 500<span class="elsevierStyleHsp" style=""></span>mL&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">b&#41;</span><p id="par0170" class="elsevierStylePara elsevierViewall">The volume analysed must be between 500 and 1<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>mL and must be exhaled in less than 4<span class="elsevierStyleHsp" style=""></span>s&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">7&#41;</span><p id="par0175" class="elsevierStylePara elsevierViewall">The patient is told to remove the nose clip and remain seated&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">8&#41;</span><p id="par0180" class="elsevierStylePara elsevierViewall">The test must be repeated until at least two values are achieved that agree within 10&#37; and below 3<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;mmHg&#46; At least 4<span class="elsevierStyleHsp" style=""></span>min must elapse between each test&#46; In patients with major obstruction it may be necessary to wait up to 10<span class="elsevierStyleHsp" style=""></span>min between tests for the gases to be completely eliminated&#46; It may be useful to ask the patient to take deep breaths so as to eliminate the gas more effectively&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">9&#41;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Calculations&#58;</p></li></ul><elsevierMultimedia ident="eq0025"></elsevierMultimedia>VA<span class="elsevierStyleInf">STPD</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>alveolar volume at STPD&#59; 60&#47;<span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>breath-hold time converted into minutes&#59; PB&#8211;47<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>barometric pressure minus water vapour pressure at 37<span class="elsevierStyleHsp" style=""></span>&#176;C&#59; ln<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>natural logarithm&#59; FA<span class="elsevierStyleSmallCaps">CO</span><span class="elsevierStyleInf">o</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>alveolar CO concentration at the start of diffusion&#59; FACO<span class="elsevierStyleInf"><span class="elsevierStyleItalic">t</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>alveolar CO concentration at the end of the test&#46;<elsevierMultimedia ident="eq0030"></elsevierMultimedia>He<span class="elsevierStyleInf"><span class="elsevierStyleItalic">E</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>exhaled He concentration&#59; He<span class="elsevierStyleInf"><span class="elsevierStyleItalic">I</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>inhaled He concentration&#59; CO<span class="elsevierStyleInf"><span class="elsevierStyleItalic">I</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>inhaled CO concentration&#59; CO<span class="elsevierStyleInf"><span class="elsevierStyleItalic">E</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>exhaled CO concentration&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Given that diffusing capacity is calculated per unit of time &#40;mL of CO absorbed per minute&#41;&#44; exact calculation of the time the patient holds his or her breath&#44; which is the time during which CO diffusion takes place&#44; is crucial&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> The Jones&#8211;Meade method for measuring the time starts counting from 30&#37; of the inhalation time and stops at 50&#37; of the alveolar gas sample collection time &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0195" class="elsevierStylePara elsevierViewall">In patients with obstruction it may be preferable to perform the test after using a bronchodilator&#44; although if heart rate increases&#44; volume per minute also increases&#44; raising DLCO&#46; For this reason it is advisable to carry out the test at least 30<span class="elsevierStyleHsp" style=""></span>min after administering the bronchodilator&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Adjustments</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Adjustment for haemoglobin &#40;Hb&#41;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Patients with anaemia have a reduced DLCO because CO uptake by erythrocytes is lower&#46; The Cotes method<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> of correction for Hb makes it possible to calculate adjusted DLCO in adult males with Hb greater than 14&#46;6<span class="elsevierStyleHsp" style=""></span>g&#47;dL or in women and in children under 15 with Hb<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>13&#46;4<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Males 15 years of age and older&#58;<elsevierMultimedia ident="eq0035"></elsevierMultimedia>Children aged &#60;15 years and women&#58;<elsevierMultimedia ident="eq0040"></elsevierMultimedia>It is advisable to put both values in the report&#58; the measured DLCO and the DLCO adjusted for Hb&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Clinical applications</span><p id="par0210" class="elsevierStylePara elsevierViewall">CO transfer can be either increased or reduced in various processes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">CO transfer is increased in situations in which there is an increase in blood volume in the pulmonary capillaries &#40;exercise&#44; left-right shunts&#41;&#44; polycythaemia and pulmonary haemorrhage &#40;falsely elevated DLCO&#41;&#46; Occasionally there is a rise in DLCO in asthmatics&#44; due to an increase in pulmonary blood volume though negative intrathoracic pressure produced after rapid inhalations&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">DLCO is decreased in patients with a reduction in alveolar volume or in diffusion defects &#40;<span class="elsevierStyleItalic">alteration of the alveolar-capillary membrane</span> &#91;interstitial lung disease&#58; idiopathic pulmonary fibrosis&#44; extrinsic allergic alveolitis&#44; scleroderma&#44; sarcoidosis&#44; asbestosis&#93; or <span class="elsevierStyleItalic">decreased pulmonary capillary blood volume</span> &#91;pulmonary embolism or primary pulmonary hypertension&#93;&#41;&#46; In pulmonary emphysema DLCO is characteristically reduced by loss of alveolar-capillary membrane surface area secondary to alveolar rupture&#44; giving rise to an increase in TLC with a decreased KCO &#40;DLCO&#47;VA&#41;&#46; In congestive heart failure the reduction in DLCO may be secondary to interstitial oedema&#46; Other causes of decreased DLCO are anaemia&#44; renal failure&#44; smoking and marijuana use&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">In patients with restrictive diseases&#44; especially in children with deformities of the rib cage or neuromuscular diseases in which normal lungs are restrictive because of deformity or muscular weakness&#44; the surface area for diffusion is relatively large per unit of pulmonary volume&#44; and for this reason DLCO may be normal&#46; The patient&#39;s DLCO&#47;VA should therefore be compared with reference values based on his or her &#40;restrictive&#41; TLC rather than his or her theoretical TLC&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In cystic fibrosis both raising and lowering of DLCO may be found&#46; Initially the transfer factor may be elevated by an increase in the amount of blood reaching the lung&#44; due to fluctuations in pleural pressure secondary to bronchial obstruction&#59; later&#44; with the onset of pulmonary heart disease&#44; pulmonary microcirculation is impaired and diffusion is gradually reduced&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Indications for the DLCO test are set out in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0240" class="elsevierStylePara elsevierViewall">In practice the main indications in paediatrics are as follows<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#58;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Monitoring of treatments that are toxic to the lungs</span><p id="par0245" class="elsevierStylePara elsevierViewall">Chemotherapy &#40;methotrexate&#44; nitrofurantoin&#44; azathioprine&#44; penicillamine&#44; cyclophosphamide and especially bleomycin&#41; can produce a major decrease in DLCO&#44; which must be monitored&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Chest radiation can cause irreversible diffusion impairment&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Treatments for autoimmune or rheumatological diseases can also impair pulmonary diffusion&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Immunosuppressants used after organ transplants have been associated with obstructive and restrictive lung disease&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Diagnosis and monitoring of patients with chronic interstitial lung disease</span><p id="par0265" class="elsevierStylePara elsevierViewall">Impairment of diffusing capacity is one of the initial signs of interstitial lung disease and a fundamental indicator of clinical course and response to treatment&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Monitoring of children with diseases that cause pulmonary bleeding</span><p id="par0270" class="elsevierStylePara elsevierViewall">In primary pulmonary haemosiderosis&#44; Goodpasture syndrome and granulomatosis with polyangiitis&#44; an increase in diffusing capacity can predict relapse or indicate progression in asymptomatic patients&#46; Moreover&#44; pulmonary haemosiderosis that does not respond to treatment may eventually give rise to pulmonary fibrosis&#44; leading to decreased diffusion&#46;</p></span></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The diffusion capacity is the technique that measures the ability of the respiratory system for gas exchange&#44; thus allowing a diagnosis of the malfunction of the alveolar-capillary unit&#46; The most important parameter to assess is the CO diffusion capacity &#40;DLCO&#41;&#46; New methods are currently being used to measure the diffusion using nitric oxide &#40;NO&#41;&#46; There are other methods for measuring diffusion&#44; although in this article the single breath technique is mainly referred to&#44; as it is the most widely used and best standardised&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Its complexity&#44; its reference equations&#44; differences in equipment&#44; inter-patient variability and conditions in which the DLCO is performed&#44; lead to a wide inter-laboratory variability&#44; although its standardisation makes this a more reliable and reproductive method&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The practical aspects of the technique are analysed&#44; by specifying the recommendations to carry out a suitable procedure&#44; the calibration routine&#44; calculations and adjustments&#46; Clinical applications are also discussed&#46; An increase in the transfer of CO occurs in diseases in which there is an increased volume of blood in the pulmonary capillaries&#44; such as in polycythemia and pulmonary haemorrhage&#46; There is a decrease in DLCO in patients with alveolar volume reduction or diffusion defects&#44; either by altered alveolar-capillary membrane &#40;interstitial diseases&#41; or decreased volume of blood in the pulmonary capillaries &#40;pulmonary embolism or primary pulmonary hypertension&#41;&#46; Other causes of decreased or increased DLCO are also highlighted&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La capacidad de difusi&#243;n es la t&#233;cnica que mide la capacidad del aparato respiratorio para realizar el intercambio gaseoso y as&#237; diagnosticar la disfunci&#243;n de la unidad alv&#233;olo-capilar&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El par&#225;metro m&#225;s importante a evaluar es la capacidad de difusi&#243;n del CO &#40;DLCO&#41;&#46; Actualmente hay nuevos m&#233;todos para medir la capacidad de difusi&#243;n utilizando &#243;xido n&#237;trico &#40;NO&#41;&#46; Existen diferentes m&#233;todos de medida&#44; aunque en este art&#237;culo nos referiremos sobre todo a la t&#233;cnica de la respiraci&#243;n &#250;nica&#44; la m&#225;s utilizada y mejor estandarizada&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Su complejidad&#44; sus ecuaciones de referencia&#44; las diferencias en equipamiento&#44; la variabilidad interpacientes y las condiciones en las que se realiza hacen que exista una gran variabilidad interlaboratorio&#44; habi&#233;ndose realizado estandarizaciones para hacer este m&#233;todo m&#225;s fiable y reproducible&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se analizan los aspectos pr&#225;cticos de la t&#233;cnica&#44; especificando las recomendaciones para la realizaci&#243;n de un procedimiento adecuado&#44; sistem&#225;tica de calibraci&#243;n y c&#225;lculos y ajustes necesarios&#46; Tambi&#233;n se exponen sus aplicaciones cl&#237;nicas&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se produce un aumento de la transferencia de CO en las enfermedades en las que existe un aumento del volumen sangu&#237;neo en los capilares pulmonares&#44; en la policitemia y en la hemorragia pulmonar&#46; Existe una disminuci&#243;n de la DLCO en los pacientes con reducci&#243;n del volumen alveolar o en los defectos de difusi&#243;n&#44; ya sea por alteraci&#243;n de la membrana alv&#233;olo-capilar &#40;enfermedad intersticial&#41; o por disminuci&#243;n del volumen de sangre en los capilares pulmonares &#40;embolia pulmonar o hipertensi&#243;n pulmonar primaria&#41;&#46; Tambi&#233;n se exponen otras causas de disminuci&#243;n o aumento de la DLCO&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Posadas AS&#44; Asensi JRV&#44; de MirMessa I&#44; Prado OS&#44; Larramona H&#46; Medici&#243;n de la difusi&#243;n de CO &#40;II&#41;&#58; estandarizaci&#243;n y criterios de calidad&#46; An Pediatr &#40;Barc&#41;&#46; 2015&#59;83&#58;137&#46;e1&#8211;137&#46;e7&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Structure of the gas exchange barrier&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Graphic illustration of the Ogilvie and Jones&#8211;Meade methods for calculating breath-hold time during the DLCO manoeuvre&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Extrapulmonary reduction in alveolar volume</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Reduced respiratory effort or muscular debility&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thoracic deformities preventing full inflation of the thorax&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Situations involving reduction of the CO-Hb reaction</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pulmonary embolism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Changes in haemoglobin&#39;s binding properties &#40;carboxyhaemoglobin&#44; increased FiO2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Conditions that alter the alveolar-capillary membrane and the CO-Hb binding&#44; reducing DLCO</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pulmonary resection &#40;there may be a compensating increase in the CO-Hb reaction&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Emphysema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Interstitial lung disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pulmonary oedema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pulmonary vasculitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pulmonary hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Situations that increase the CO-Hb reaction and raise DLCO</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Polycythaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Left-right shunt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pulmonary haemorrhage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Asthma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Changes in the Hb binding properties &#40;reduced FiO2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M&#252;ller&#39;s manoeuvre &#40;reduction in intrathoracic pressure&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exercise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Supine position&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Obesity&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">1&#46; Evaluation and followup of diseases affecting lung parenchyma &#40;those associated with drug reactions&#44; pneumoconiosis or sarcoidosis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&#46; Evaluation and followup of emphysema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&#46; Differentiating between chronic bronchitis&#44; emphysema and asthma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">4&#46; Assessment of pulmonary involvement in systemic diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">5&#46; Assessment of cardiovascular diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">6&#46; Prediction of arterial desaturation during exercise in some patients with lung disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">7&#46; Assessment and quantification of the degree of disability associated with pulmonary fibrosis or with emphysema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">8&#46; Assessment of the pulmonary effects of chemotherapy agents or other drugs that induce pulmonary dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">9&#46; Assessment of pulmonary haemorrhage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">10&#46; As an early indicator of certain pulmonary infections that cause diffuse pneumonitis &#40;e&#46;g&#46;&#44; <span class="elsevierStyleItalic">Pneumocystis</span> pneumonia&#41;&nbsp;\t\t\t\t\t\t\n
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:26 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Single-breath carbon monoxide diffusing capacity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Wanger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:4 [
                        "titulo" => "Pulmonary function testing"
                        "paginaInicial" => "145"
                        "paginaFinal" => "173"
                        "serieFecha" => "1996"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Standardisation of the single-breath determination of carbon monoxide uptake in the lung"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; MacIntyre"
                            1 => "R&#46;O&#46; Crapo"
                            2 => "G&#46; Viegi"
                            3 => "D&#46;C&#46; Johnson"
                            4 => "C&#46;P&#46; van der Grinten"
                            5 => "V&#46; Brusasco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.05.00034905"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2005"
                        "volumen" => "26"
                        "paginaInicial" => "720"
                        "paginaFinal" => "735"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16204605"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diffusing capacity for nitric oxide&#58; reference values and dependence on alveolar volume"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I&#46; Van der Lee"
                            1 => "P&#46; Zanen"
                            2 => "N&#46; Stigter"
                            3 => "J&#46;M&#46; van den Bosch"
                            4 => "J&#46;W&#46; Lammers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2006.12.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2007"
                        "volumen" => "101"
                        "paginaInicial" => "1579"
                        "paginaFinal" => "1584"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17229562"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The TLNO&#47;TLCO ratio in pulmonary function test interpretation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;M&#46; Hughes"
                            1 => "I&#46; van der Lee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00082112"
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2013"
                        "volumen" => "41"
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2015.06.012

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	12	17	29
2024 October	68	35	103
2024 September	78	50	128
2024 August	98	86	184
2024 July	117	43	160
2024 June	83	46	129
2024 May	69	48	117
2024 April	87	42	129
2024 March	74	31	105
2024 February	52	34	86
2024 January	79	28	107
2023 December	79	42	121
2023 November	120	34	154
2023 October	98	75	173
2023 September	80	37	117
2023 August	81	27	108
2023 July	99	33	132
2023 June	103	34	137
2023 May	141	31	172
2023 April	82	33	115
2023 March	175	33	208
2023 February	176	23	199
2023 January	96	37	133
2022 December	132	29	161
2022 November	140	37	177
2022 October	103	57	160
2022 September	136	35	171
2022 August	131	53	184
2022 July	130	45	175
2022 June	95	50	145
2022 May	135	37	172
2022 April	115	48	163
2022 March	125	77	202
2022 February	142	45	187
2022 January	195	34	229
2021 December	163	66	229
2021 November	133	68	201
2021 October	103	66	169
2021 September	122	62	184
2021 August	113	50	163
2021 July	135	60	195
2021 June	126	69	195
2021 May	147	51	198
2021 April	619	104	723
2021 March	202	50	252
2021 February	158	29	187
2021 January	182	57	239
2020 December	131	44	175
2020 November	110	25	135
2020 October	105	31	136
2020 September	89	31	120
2020 August	98	15	113
2020 July	98	47	145
2020 June	81	14	95
2020 May	124	41	165
2020 April	156	35	191
2020 March	166	33	199
2020 February	188	27	215
2020 January	200	29	229
2019 December	251	23	274
2019 November	219	18	237
2019 October	267	22	289
2019 September	221	24	245
2019 August	183	17	200
2019 July	172	40	212
2019 June	160	23	183
2019 May	201	27	228
2019 April	191	34	225
2019 March	112	27	139
2019 February	87	21	108
2019 January	101	19	120
2018 December	90	35	125
2018 November	148	28	176
2018 October	242	22	264
2018 September	126	24	150
2018 July	5	0	5
2018 June	5	0	5
2018 May	12	0	12
2018 April	52	0	52
2018 March	54	0	54
2018 February	31	0	31
2018 January	29	0	29
2017 December	34	0	34
2017 November	35	0	35
2017 October	27	0	27
2017 September	30	0	30
2017 August	45	0	45
2017 July	45	0	45
2017 June	57	16	73
2017 May	57	13	70
2017 April	119	15	134
2017 March	38	8	46
2017 February	102	12	114
2017 January	18	12	30
2016 December	56	9	65
2016 November	95	9	104
2016 October	131	15	146
2016 September	128	5	133
2016 August	64	8	72
2016 July	37	6	43

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