Correlation between chest computed tomography findings and pulmonary function test results in the post-recovery phase of COVID-19

ABSTRACT Objective The radiological and functional lung sequelae in COVID-19 survivors remain unclear. We compared the chest computed tomography findings of COVID-19 patients with normal and abnormal pulmonary function test results in the post-recovery phase. Methods The data of consecutive patients who underwent pulmonary function tests and chest computed tomography within 14 days after recovery from COVID-19 at two medical centers between May and October 2020 were collected retrospectively. Two thoracic radiologists who were blinded to the clinical information and pulmonary function test results classified the patients according to the computed tomography features, evidence of fibrotic-like changes, and semi-quantitative quantification of the extent of pulmonary abnormalities. The clinical characteristics and computed tomography findings of patients with normal pulmonary function test results were compared with those of patients with abnormal results. Results A total of 101 COVID-19 survivors, comprising 48 ambulatory and 53 hospitalized patients, were included at a median of 95 days from initial symptom onset. Computed tomography revealed fibrotic-like changes in 10.9% of patients. A reduction in the diffusion capacity of carbon monoxide was the most common lung function abnormality (19.8%). Abnormal diffusion capacity of carbon monoxide was associated with the presence and extension of lung opacities on chest computed tomography scans and fibrotic pulmonary abnormalities. The sensitivity, specificity, and accuracy of reduced diffusion capacity of carbon monoxide for detecting fibrotic-like pulmonary changes on chest computed tomography scans were 72.7%, 87.8%, and 86.1%, respectively. Conclusion Our study suggests that the presence of an abnormal diffusion capacity of carbon monoxide in the post-recovery phase of COVID-19 is associated with a greater risk of long-term parenchymal lung disease, as evidenced by the presence of fibrotic-like changes on chest computed tomography scans, such as traction bronchiectasis and architectural distortion.

Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion / Linfangioleiomiomatose: níveis circulantes de FGF23 e difusão pulmonar

ABSTRACT Objective: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. Methods: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. Results: The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). Conclusions: Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.

RESUMO Objetivo: A linfangioleiomiomatose (LAM) é uma doença rara e destrutiva dos pulmões com um número limitado de determinantes da atividade da doença, que são uma necessidade crítica para ensaios clínicos. O FGF23 já foi implicado em várias doenças pulmonares crônicas. O nosso objetivo foi determinar a associação entre os níveis séricos de FGF23 e a função pulmonar em uma coorte de pacientes com LAM. Métodos: Estudo descritivo unicêntrico no qual foram recrutados indivíduos com LAM e controles com doenças pulmonares não declaradas. Os níveis séricos de FGF23 foram medidos em todos os indivíduos. Os dados clínicos, incluindo testes de função pulmonar, foram obtidos retrospectivamente a partir dos prontuários eletrônicos dos indivíduos com LAM. As associações entre os níveis de FGF23 e as características clínicas da LAM foram exploradas por meio do teste de hipóteses não paramétrico. Resultados: A amostra incluiu 37 indivíduos com LAM e 16 controles. Os níveis de FGF23 foram mais altos no grupo LAM do que no grupo controle. No grupo LAM, níveis de FGF23 acima do ponto de corte ideal distinguiram 33% dos indivíduos com níveis não diagnósticos de VEGF-D. Níveis mais baixos de FGF23 estavam associados à DLCO comprometida (p = 0,04), particularmente naqueles com comprometimento isolado da difusão e sem outras alterações espirométricas (p = 0,04). Conclusões: Nossos resultados sugerem que o FGF23 está associado a alterações na difusão pulmonar em pacientes com LAM e potencialmente indicam novos mecanismos de patogênese da LAM. O FGF23 isoladamente ou em combinação com outras moléculas precisa ser validado como um biomarcador da atividade da LAM em futuras pesquisas clínicas.

Design and Verification of Lung Diffusion Function Detection System / 中国医疗器械杂志

A lung diffusion function detection system is designed. Firstly, the controllable collection of air, test gas source and calibration gas source was based on single-breath method measurement principle. Secondly, pulmonary diffusing capacity for carbon monoxide (DlCO) was calculated by gas concentration measured by the non-dispersive infrared sensor to measure, the gas flow measured by the differential pressure sensor, and the temperature, humidity and atmospheric pressure sensors to test and evaluate the quantitative detection and evaluation of lung diffusion function. Moreover, a preliminary verification of the lung diffusion function detection system was implemented, and the results showed that the error of the lung carbon monoxide diffusion and the alveolar volume did not exceed 5%. Therefore, the system has high accuracy and is of great value for early screening and accurate assessment of COPD.

Fisiología respiratoria: difusión de gases / Gas diffusion

El principal objetivo del sistema respiratorio es permitir un adecuado aporte de oxígeno y remoción del dióxido de carbono. Para esto, debe ocurrir una adecuada difusión de gases en la membrana alvéolo-capilar, proceso pasivo en el que el oxígeno se mueve hacia el capilar y el dióxido de carbono hacia el alvéolo. La ley de Fick establece los determinantes de la difusión, los que están dados por propiedades de la membrana alvéolo-capilar y de los gases. Las características únicas de la membrana alvéolo-capilar favorecen la difusión de gases, pero es el gradiente de presión parcial de los gases el principal determinante. El oxígeno pasa fácilmente por la membrana alvéolo-capilar y se une rápidamente a la hemoglobina, saturándola, cuando se iguala la presión parcial de oxígeno alveolar y la capilar se detiene la difusión de este gas; por lo que la difusión de oxígeno en reposo está limitada por perfusión. El dióxido de carbono difunde 20 veces más rápido que el oxígeno en la membrana alvéolo-capilar, y aunque su gradiente de presión sea menor, el equilibrio se logra aproximadamente en el mismo tiempo. La difusión del oxígeno es más lenta que la del dióxido de carbono debido a su menor solubilidad. En condiciones patológicas tanto el oxígeno como el dióxido de carbono pueden ser limitados por difusión. Para medir la capacidad de difusión la técnica más utilizada es la capacidad de difusión de monóxido de carbono, ya que este gas solo está limitado por difusión.

The main objective of the respiratory system is allowing an adequate supply of oxygen and the removal of carbon dioxide from the tissues. To achieve this, an adequate diffusion of gases must occur in the alveolus-capillary membrane, which is a passive process in which oxygen moves towards the capillary and carbon dioxide towards the alveolus. Fick's law establishes the determinants of diffusion, which are given by properties of the alveolar-capillary membrane and properties of gases. The unique characteristics of the capillary-alveolar membrane favor the diffusion of gases, but it is the partial pressure gradient of the gases the main determinant. Oxygen passes easily through the alveolar-capillary membrane and rapidly binds to hemoglobin, saturating it. When the partial pressure of alveolar oxygen is matched, the diffusion of this gas stops; therefore, the diffusion of oxygen is limited by perfusion. Carbon dioxide diffuses 20 times faster than oxygen in the capillary-alveolar membrane, and although its pressure gradient is less than oxygen, equilibrium is achieved in approximately the same time. The diffusion of oxygen is slower than that of carbon dioxide due to its lower solubility. Under pathological conditions both oxygen and carbon dioxide can be diffusion-limited. To measure the diffusion capacity, the most used technique is the carbon monoxide diffusion capacity, since this gas is only limited by diffusion.

Valores de referência para a difusão do monóxido de carbono (fator de transferência) em uma amostra brasileira da raça branca / Reference values for the carbon monoxide diffusion (transfer factor) in a brazilian sample of white race

RESUMO Objetivo Derivar valores de referência em adultos brancos para a difusão do monóxido de carbono (DCO) em uma amostra de diferentes locais do Brasil por um mesmo modelo de equipamento (Sensormedics) e comparar os resultados com os derivados pelas equações de Crapo, Miller e Neder, e da proposta pelo Global Lung Initiative (GLI). Métodos Os testes foram realizados de acordo com as normas sugeridas pela ATS/ERS, em 2005, em seis cidades brasileiras, em 120 voluntários adultos de cada sexo, não fumantes, sem anemia referida e sem doenças pulmonares ou cardíacas. Os previstos foram derivados por regressões lineares e as diferenças entre os valores previstos por alguns autores e os observados no estudo atual foram calculadas. Resultados Nos homens, a idade variou de 25 a 88 anos e a estatura, de 156 a 189 cm. Nas mulheres, a idade variou de 21 a 92 anos e a estatura, de 140 a 176 cm. A DCO se correlacionou de maneira significativa positivamente com a estatura e negativamente com a idade. Os valores previstos pelas equações de Crapo, Neder e Miller foram maiores em comparação aos obtidos pelo estudo atual (p<0,01) em ambos os sexos. Nos homens, os valores não diferiram quando comparados aos calculados pelo GLI (p=0,29); nas mulheres, os valores derivados pelo GLI foram levemente maiores: 0,99 mL/min/mmHg (p<0,01). Conclusões Novos valores previstos para a DCO foram derivados em uma amostra de adultos brancos no Brasil. Os valores previstos são semelhantes aos compilados pelas equações GLI e diferem de equações propostas anteriormente.

ABSTRACT Objective To derive reference values from white race adults, for DCO in a sample from different sites in Brazil, through the same equipment model (Sensormedics), and compare the results with the derivatives from Crapo, Miller, Neder equations and from the Global Lung Initiative (GLI) proposal. Methods The tests were performed according to the norms suggested by ATS/ERS in 2005 in six Brazilian cities, with 120 adult volunteers of each gender, non-smokers, without referred anemia and without lung or cardio diseases. The expected values were derived from linear regressions and the differences between the values forecasted by some authors and the ones observed in the current study were calculated. Results Among men, the age varied between 25 and 88 years old, and the height varied between 140 and 176 cm. DCO was correlated significantly and positively with the height and negatively with the age. The values forecasted by Crapo, Neder, and Miller equations were higher in comparison with the ones obtained by the current study (p<0.01) in both genders. Among men, the values did not differ when compared to the ones calculated by GLI (p=0.29); among women, the values derived by GLI were slightly higher: 0.99 ml/min/mmHg (p<0.01). Conclusion new values forecasted for DCO were derived in a sample of white adults in Brazil. The forecasted values are similar to the ones complied by GLI equations and differ from the previously proposed equations.

Development of Prediction Equation of Diffusing Capacity of Lung for Koreans / 결핵

BACKGROUND: The diffusing capacity of the lung is influenced by multiple factors such as age, sex, height, weight, ethnicity and smoking status. Although a prediction equation for the diffusing capacity of Korea was proposed in the mid-1980s, this equation is not used currently. The aim of this study was to develop a new prediction equation for the diffusing capacity for Koreans. METHODS: Using the data of the Korean National Health and Nutrition Examination Survey, a total of 140 nonsmokers with normal chest X-rays were enrolled in this study. RESULTS: Using linear regression analysis, a new predicting equation for diffusing capacity was developed. For men, the following new equations were developed: carbon monoxide diffusing capacity (DLco)=−10.4433−0.1434×age (year)+0.2482×heights (cm); DLco/alveolar volume (VA)=6.01507−0.02374×age (year)−0.00233×heights (cm). For women the prediction equations were described as followed: DLco=−12.8895−0.0532×age (year)+0.2145×heights (cm) and DLco/VA=7.69516−0.02219×age (year)−0.01377×heights (cm). All equations were internally validated by k-fold cross validation method. CONCLUSION: In this study, we developed new prediction equations for the diffusing capacity of the lungs of Koreans. A further study is needed to validate the new predicting equation for diffusing capacity.

O efeito do índice de massa corpórea na função pulmonar / The effect of body mass index on pulmonary function

Objetivo: caracterizar os volumes pulmonares, a resistência das vias aéreas (Rva) e a capacidade de difusão do monóxido do carbono (DCO) em indivíduos com índice de massa corpórea (IMC) normal, pré-obesos, obesidade classe I, obesidade classe II e obesidade classe III. Metodologia: estudo retrospectivo, quantitativo e transversal. A amostra foi constituída por 304 indivíduos de ambos os gêneros com suspeita ou diagnóstico clínico de asma, com IMC?25 kg/m2 e sem alterações nas provas funcionais respiratórias e por 95 indivíduos de ambos os gêneros, saudáveis e com IMC.

Objective: to characterize lung volumes, airway resistance (AWR), and carbon monoxide diffusion capacity (CMD) in individuals with normal, pre obese, class I obesity, class II obesity, and class III obesity body mass index (BMI). Methodology: this was a retrospective, quantitative, and cross-sectional study. The sample consisted of 304 individuals of both genders with suspicion or clinical diagnosis of asthma, with BMI ? 25 kg/m2, and without alterations in respiratory functional tests and 95 healthy and with normal BMI individuals of both genders.

Proposal of New Criteria for Assessing Respiratory Impairment / 결핵및호흡기질환

Social welfare services for respiratory-disabled persons in Korea are offered based on the respiratory impairment grade, which is determined by 3 clinical parameters; dyspnea, forced expiratory volume in 1 second (FEV1), and arterial oxygen tension. This grading system has several limitations in the objective assessment of respiratory impairment. We reviewed several guidelines for the evaluation of respiratory impairment and relevant articles. Then, we discussed a new grading system with respiratory physicians. Both researchers and respiratory physicians agreed that pulmonary function tests are essential in assessing the severity of respiratory impairment, forced vital capacity (FVC), FEV1 and single breath diffusing capacity (DLco) are the primarily recommended tests. In addition, we agreed that arterial blood gas analysis should be reserved for selected patients. In conclusion, we propose a new respiratory impairment grading system utilizing a combination FVC, FEV1 and DLco scores, with more social discussion included.

Pulmonary function in patients with type 2 diabetes mellitus / 中国病理生理杂志

AIM: To evaluate the pulmonary function in patients with type 2 diabetes mellitus in order to identify whether the lung is a target organ of chronic pathologic changes in diabetes mellitus. METHODS: Pulmonary ventilation function and diffusion capacity were studied in 107 patients with type 2 diabetes mellitus and 61 healthy subjects matched for age and sex. Glycosylated hemoglobin (HbA1c), urine albumin excretion rate (AER), fundus examination and nerve conduction velocity were included as parameters of glycemic control and diabetic microangiopathies. RESULTS: Pulmonary ventilation function was similar in type 2 diabetic group and the control. Compared with the control, carbon monoxide diffusion capacity (DLCO) and DLCO corrected by alveolar volume (DLCO/VA) were significantly lower in type 2 diabetic group (P<0.05). DLCO and DLCO/VA were inversely correlated with microangiopathy score (r: -0.291, -0.324, respectively, P<0.01). Furthermore, DLCO/VA was negatively correlated with age and duration of diabetes mellitus (r: -0.269, -0.236, respectively, P<0.05). CONCLUSIONS: Pulmonary ventilation function is normal in patients with type 2 diabetes mellitus, but their diffusion capacity is impaired. It suggests that the lung may also be the target organ of the chronic pathologic changes of diabetes mellitus.

Effect of dexamethasone on pulmonary diffusion in patients undergoing cardiac valve replacement under cardiopulmonary bypass / 中华麻醉学杂志

Objective To investigate the effect of dexamethasone on the pulmonary gas exchange in patients undergoing cardiac valve replacement under cardiopulmonary bypass(CPB).Methods Forty ASAⅡorⅢpatients aged 29-47 yrs weighing 50-69 kg undergoing cardiac valve replacement under CPB were randomly divided into 2 groups(n=20 each):dexamethasone group received dexamethasone 0.5 mg?kg~(-1) after induction of anesthesia and control group received normal saline(NS).Blood samples were taken before operation(T_0) immediately before CPB(T_1)and immediately after discontinuation of CPB(T_2)for determination of plasma total and active matrix metallo-proteinase-9(MMP-9)concentration(by enzyme-linked immuno-absorbent and fluorometric enzyme-linked immuno-absorbent assay respectively)and MMP-9 gene expression(RT-PCR).Blood samples were taken from radial artery at T_1 and T_2 for blood gas analysis.A-aDO_2 was calculated.Results MMP-9 gene expression and plasma total and active MMP-9 concentrations were significantly increased at T_2 as compared with those at T_0 in both groups and were significantly lower in dexamethasone group than in control group(P＜0.05 or 0.01).The A-aDO_2 at T_2 was significantly smaller in dexamethasone group than in control group.Conclusion Dexamethasone can inhibit the increase in gene expression,protein synthesis and activation of MMP-9 and decrease in gas exchange across alveolar-capillary membrane caused by CPB and protect the lungs during open heart surgery performed under CPB.