Addressing Reduced Laboratory-Based Pulmonary Function Testing During a Pandemic.

To reduce the spread of the severe acute respiratory syndrome coronavirus 2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. Because these mitigation strategies may be necessary for the next 6 to 18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFT, which includes spirometry, lung volume, and diffusion capacity measurement, is essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions. Both traditional and innovative alternatives to conventional testing must now be explored. These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, and novel digital health tools such as smartphone microphone spirometers and mobile health technologies along with integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options comes important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the coronavirus disease 19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease. The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.

The measurement of DLNO and DLCO: A manufacturer's perspective.

The simultaneous measurement of the lung transfer factor for carbon monoxide (DLCO) and nitric oxide (DLNO) is now available as a powerful method for studying the alveolar-capillary gas exchange. However, application of the DLNO-CO technique in daily settings is still limited by some technical drawbacks. This paper provides a manufacturer's overview of the measuring principles, technical challenges and current available solutions for implementing the DLNO-CO measurement in to a marketed device. This includes the recent developments in technology for NO sensors, latest findings on NO uptake and new statistical methods.

Long-Term Stability of a Portable Carbon Monoxide Single-Breath Diffusing Capacity Instrument.

BACKGROUND: The 2005 American Thoracic Society/European Respiratory Society guidelines for single-breath diffusing capacity of the lung for carbon monoxide (DLCO) recommend a weekly biological control test and/or DLCO simulator to detect instrument error drift. Very little has been published regarding the results of such a quality assurance program. Our aim was to analyze the long-term stability of a portable DLCO instrument. METHODS: We used a new EasyOne Pro system and checked its accuracy using a DLCO simulator with 2 reference gases (concentration A: carbon monoxide [CO] = 0.1% and helium = 6.52%; concentration B: CO = 0.08% and helium = 7.21%) during the first 3 y of use in our large clinical laboratory. To detect instrument drift, a healthy woman (MSC), age 43 y old at baseline, tested herself every week during this period of time. RESULTS: More than 6,000 spirometry and 5,000 DLCO maneuvers were done using this instrument for patients during these 3 y. There were no failures in the daily volume and flow checks or the CO and helium calibration checks performed automatically by the instrument. The differences between the simulator DLCO and the measured DLCO were -0.91 ± 1.33 mL/min/mm Hg and -0.61 ± 1.45 mL/min/mm Hg for concentration A and concentration B, respectively. The results of the 110 biological control tests were: mean 30.8 ± 1.7 mL/min/mm Hg (95% CI 30.5-31.1), coefficient of variation of 5.4% in DLCO, and repeatability of 2.5 mL/min/mm Hg. Only 4 measurements were outside ±3 mL/min/mm Hg (3.6%). Her mean alveolar volume was 4.2 ± 0.25 L with coefficient of variation of 6.2%; her inspired volume was 3.05 ± 0.14 L, and coefficient of variation = 4.5%. CONCLUSIONS: Measurements of DLCO were stable over the 3-y period without any need for manual recalibration of the instrument. The biological control was as good as the DLCO simulator to evaluate this kind of device in a long-term laboratory quality control program.

Medición de la difusión de CO (II): estandarización y criterios de calidad / Measurement of CO diffusion capacity (II): Standardization and quality criteria

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

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 standardized. 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 standardization makes this a more reliable and reproductive method. The practical aspects of the technique are analyzed, 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 the polycythemia and pulmonary hemorrhage. 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

O impacto dos valores previstos nos testes de função pulmonar / The impact of predicted values in pulmonary function tests

A interpretação dos testes de função pulmonar é resultado da comparação de valores obtidos com valores previstos para um determinado indivíduo. Os valores previstos são obtidos através de equações de referência, sendo estas determinadas por dados antropométricos e demográficos dos indivíduos. A presente revisão de literatura pretende identificar quais as equações referência mais utilizadas para os testes de função pulmonar, comparar estudos entre equações com ênfase nas publicações de equações de referência brasileiras.

Lung function test interpretation is based on the comparison between values measured according to the predicted values for each individual. The predicted values come from reference equations, which depend on anthropometric and demographic data of individuals. The present review aims to identify the most commonly used reference equations for pulmonary function tests, interpret comparative studies between equations and emphasizes publications with Brazilian reference equations.

Long-term intersession variability for single-breath diffusing capacity.

BACKGROUND: Characterizing long-term diffusing capacity (DL(CO)) variability is important in assessing quality control for DL(CO) equipment and patient management. Long-term DL(CO) variability has not been reported. OBJECTIVES: It was the aim of this study to characterize long-term variability of DL(CO) in a cohort of biocontrols and to compare different methods of selecting a target value. METHODS: Longitudinal DL(CO) monitoring of biocontrols was performed as part of the inhaled insulin development program; 288 biocontrols were tested twice monthly for up to 5 years using a standardized technique. Variability, expressed either as percent change or DL(CO) units, was assessed using three different target values. RESULTS: The 90th percentile for mean intersession change in DL(CO) was between 10.9 and 15.8% (2.6-4.1 units) depending on the target value. Variability was lowest when the mean of all DL(CO) tests was used as the target value and highest when the baseline DL(CO) was used. The average of the first six DL(CO) tests provided an accurate estimate of the mean DL(CO) value. Using this target, the 90th percentile for mean intersession change was 12.3% and 3.0 units. Variability was stable over time and there were no meaningful associations between variability and demographic factors. CONCLUSIONS: DL(CO) biocontrol deviations >12% or >3.0 units, from the average of the first six tests, indicate that the instrument is not within quality control limits and should be carefully evaluated before further patient testing.

Facing the noise: addressing the endemic variability in D(LCO) testing.

Single-breath diffusing capacity of the lung for carbon monoxide (D(LCO)) is a common pulmonary function test that measures the ability of the lung to exchange gas across the alveolar-capillary interface. D(LCO) testing is used to narrow the differential diagnosis of obstructive and restrictive lung disease, to aid in disability and transplant assessment, and to monitor medication toxicity. The variability in the measurement limits the utility of the test. Variability is attributable to differences in equipment, testing conditions, patient factors, and reference equations. Laboratories can minimize variability by ensuring that equipment meets recommended standards, implementing effective quality control programs, standardizing testing conditions and testing procedures, and accounting for pertinent patient characteristics.

Multi-wavelength pulse oximeter is not suitable for adjusting D(LCO) measurements.

BACKGROUND: Diffusing capacity of the lung for carbon monoxide (D(LCO)) can be affected by abnormal hemoglobin (Hb) or carboxyhemoglobin (COHb) levels. Predicted D(LCO) can be adjusted to reflect abnormal Hb or COHb levels. Until recently, blood sampling was required to determine Hb and COHb levels, but a new pulse oximeter, the Masimo RAD-57, can measure Hb and COHb noninvasively. We hypothesized that there would be no significant difference between the invasive and noninvasive Hb and COHb measurements for adjusting D(LCO). METHODS: In patients referred to our university hospital for D(LCO) testing, we simultaneously took arterial blood gas samples and measured Hb and COHb with the RAD-57 (SpHb and SpCOHb, respectively). We analyzed the paired values and the Hb-adjusted and COHb-adjusted predicted D(LCO) values with t tests and Bland-Altman plots. We compared the differences in predicted D(LCO) to a clinical threshold of 3 mL/min/mm Hg. RESULTS: SpHb differed from Hb measured via arterial blood analysis (12.1 ± 2.4 g/dL vs 13.3 ± 2.1 g/dL, P < .001). SpCOHb did not differ significantly from COHb (ie, measured via arterial blood analysis) (2.1 ± 4.0 vs 2.5 ± 2.3, P = .25), but there was wide variability. There were small but statistically significant differences in the adjusted predicted D(LCO), depending on whether blood or pulse oximetry values were used. Predicted D(LCO) adjusted for both Hb and COHb was 22.5 ± 4.8 mL/min/mm Hg measured with the RAD-57 and 23.5 ± 4.5 mL/min/mm Hg via arterial blood analysis (P < .001). The limits of agreement for pulse oximetry adjusted D(LCO) exceeded the clinical threshold of 3 mL/min/mm Hg for Hb adjustments and combined Hb + COHb. Predicted D(LCO) values differed by > 3 mL/min/mm Hg in 17% of patients. CONCLUSIONS: Pulse oximetry may be of limited usefulness for adjusting either predicted or measured D(LCO) values, but might be useful to screen patients for invasive testing, particularly if the D(LCO) is close to the lower limit of normal.

Lung diffusing capacity relates better to short-term progression on HRCT abnormalities than spirometry in mild asbestosis.

BACKGROUND: Pulmonary function tests (PFT), particularly spirometry and lung diffusing capacity for carbon monoxide (DL(CO) ), have been considered useful methods for the detection of the progression of interstitial asbestos abnormalities as indicated by high-resolution computed tomography (HRCT). However, it is currently unknown which of these two tests correlates best with anatomical changes over time. METHODS: In this study, we contrasted longitudinal changes (3-9 years follow-up) in PFTs at rest and during exercise with interstitial abnormalities evaluated by HRCT in 63 ex-workers with mild-to-moderate asbestosis. RESULTS: At baseline, patients presented with low-grade asbestosis (Huuskonen classes I-II), and most PFT results were within the limits of normality. In the follow-up, most subjects had normal spirometry, static lung volumes and arterial blood gases. In contrast, frequency of DL(CO) abnormalities almost doubled (P < 0.05). Twenty-three (36.5%) subjects increased the interstitial marks on HRCT. These had significantly larger declines in DL(CO) compared to patients who remained stable (0.88 vs. 0.31 ml/min/mm Hg/year and 3.5 vs. 1.2%/year, respectively; P < 0.05). In contrast, no between-group differences were found for the other functional tests, including spirometry (P > 0.05). CONCLUSIONS: These data demonstrate that the functional consequences of progression of HRCT abnormalities in mild-to-moderate asbestosis are better reflected by decrements in DL(CO) than by spirometric changes. These results might have important practical implications for medico-legal evaluation of this patient population.

Diffusing capacity.

The diffusing capacity for carbon monoxide (DL(CO)) is a commonly performed and clinically useful pulmonary function test that provides a quantitative measure of gas transfer in the lungs. It is valuable for evaluating and managing patients with a wide variety of pulmonary disorders, especially patients with interstitial lung disease, pulmonary vascular disease, and obstructive lung disease. Important aspects of the DL(CO) test are discussed including the physiologic principles governing diffusion, testing technique and equipment, technical and physiologic factors influencing DL(CO) variability, DL(CO) test interpretation, and the clinical utility of DL(CO) measurement.

Estrategias de interpretación de las pruebas de función pulmonar / No disponible

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Instrument accuracy and reproducibility in measurements of pulmonary function.

BACKGROUND: The objective of the study was to quantify the accuracy and reproducibility of five commercially available pulmonary function test (PFT) instruments (Collins CPL [Ferraris Respiratory; Louisville, CO]; Morgan Transflow Test PFT System [Morgan Scientific; Haverhill, MA]; SensorMedics Vmax 22D [VIASYS Healthcare; Yorba Linda, CA]; Jaeger USA Masterscreen Diffusion TP [VIASYS Healthcare]; and Medical Graphics Profiler DX System [Medical Graphics Corp; St. Paul, MN]) that are associated with spirometry and the measurement of pulmonary diffusing capacity. METHODS: In a multifactor, single-center, repeated-measures, full factorial 90-day study, a pulmonary waveform generator and a single-breath simulator of diffusing capacity of the lung for carbon monoxide (Dlco) were used to perform simulations of FVC and Dlco maneuvers. Accuracy was assessed as the difference between the observed and simulated values. Reproducibility was determined as the coefficient of variation of all measurements made during the study. RESULTS: All instruments demonstrated a high degree of accuracy in the measurement of FVC and FEV(1). Overall, the accuracies associated with the measurement of peak flow, forced expiratory flow, mid-expiratory phase, and diffusing capacity were generally lower and more variable among the instruments tested. The coefficients of variation of Dlco measurements over 90 days were higher than those observed for spirometry. CONCLUSIONS: This study demonstrates the feasibility of assessing the accuracy and reproducibility of modern PFT instruments using simulation testing. Our results provide an assessment of the component of PFT accuracy and reproducibility that is due to instrumentation alone.

Measurement of single breath-hold carbon monoxide diffusing capacity in healthy infants and toddlers.

We describe a method for measuring carbon monoxide diffusing capacity (DL(CO)) and alveolar volume (V(A)) in sleeping infants, using a single 4-sec breath-hold technique. The breath-hold maneuver is obtained by inducing a respiratory pause of the respiratory system. Several inflations of the respiratory system with room air to a lung volume with an airway pressure of 30 cmH2O (V30) inhibit inspiratory effort. The respiratory system is then inflated with a test gas containing helium and a stable isotope of carbon monoxide (C18O), and a respiratory pause is maintained for 4 sec and followed by passive expiration to functional residual capacity. Concentrations of helium and C18O are continuously measured with a mass spectrometer. Twelve healthy infants between 6-22 months of age were evaluated. For 9 of 12 subjects, duplicate measurements of alveolar volume at 30 cmH2O (V(A30)) and DL(CO) were within 10%, which are the recommendations for older children and adults. Among these 9 subjects, values of V(A30) and DL(CO) increased with increasing body length (r2 = 0.82 and 0.79, respectively). The remaining 3 subjects had two values within 10-15%. Measurement of V(A) and DL(CO) with the single breath-hold technique at an elevated lung volume offers the potential to assess growth and development of the lung parenchyma early in life.