The Investigation of Pulmonary Abnormalities using Hyperpolarised Xenon Magnetic Resonance Imaging in Patients with Long-COVID
James T. GristGuilhem CollierHuw WaltersMitchell ChenGabriele Abu EidAviana LawsViolet MatthewsKenneth JacobSusan CrossAlexandra EvesMarianne DurantAnthony McIntyreRoger ThompsonRolf F. SchulteBetty RamanPeter A. RobbinsJim M. WildEmily FraserFergus Gleeson
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Abstract Background Long-COVID is an umbrella term used to describe ongoing symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is one of the most common and can persist for months after the initial infection. Investigations including Computed Tomography (CT), and physiological measurements (lung function tests) are usually unremarkable. The mechanisms driving breathlessness remain unclear, and this may be hindering the development of effective treatments. Methods Eleven non-hospitalised Long-COVID (NHLC, 4 male), 12 post-hospitalised COVID-19 (PHC, 10 male) patients were recruited from a Post-COVID Assessment clinic, and thirteen healthy controls (6 female) were recruited to undergo Hyperpolarized Xenon Magnetic Resonance Imaging (Hp-XeMRI). NHLC and PHC participants underwent contemporaneous CT, Hp-XeMRI, lung function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Statistical analysis included group and pair-wise comparisons between patients and controls, and correlations between patient clinical and imaging data. Results NHLC and PHC patients were 287 ± 79 [range 190-437] and 149 ± 68 [range 68-269] days from infection, respectively. All NHLC patients had normal CT scans, and the PHC had normal or near normal CT scans (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively). There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04) but no differences in other measurements of lung function. There were significant differences in RBC:TP mean between volunteers (0.45 ± 0.07, range [0.33-0.55]) and PHC (0.31 ± 0.11, [range 0.16-0.37]) and NHLC (0.35 ± 0.09, [range 0.26-0.58]) patients, but not between NHLC and PHC (p = 0.26). Conclusion There are RBC:TP abnormalities in NHLC and PHC patients, with NHLC patients also demonstrating lower TLco than PHC patients despite their having normal CT scans. These abnormalities are present many months after the initial infection. Summary statement Hyperpolarized Xenon MRI and TLco demonstrate significantly impaired gas transfer in non-hospitalised long-COVID patients when all other investigations are normal. Key results There are significant differences in RBC:TP mean between healthy controls and PHC/NHLC patients (0.45 ± 0.07, range [0.33-0.55], 0.31 ± 0.11, [range 0.16-0.37], 0.35 ± 0.09, [range 0.26-0.58], respectively, p < 0.05 after correction for multiple comparisons) indicating a change in lung compartment volumes between groups. There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04), despite normal or near normal FEV (%) (100 ± 13% [range 72-123%] and 88 ± 21% [range 62-113%], p>0.05. There were significant differences in CT abnormalities between NHLC and PHC patients (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively) despite similarly impaired RBC:TP.Keywords:
DLCO
Significance of pulmonary function testing in the diagnosis of chronic obstructive pulmonary disease
Objective To explore the significance of pulmonary function testing in the diagnosis of chronic obstructive pulmonary disease(COPD).Methods Sixty patients with COPD for lung function testing while 74 cases of normal controls to observe the characteristics of pulmonary function of patients with COPD.Results The proportion of mild,moderate,severe and very severe of COPD patients was 23.7％,42.4％,25.4％ and 8.5％,and the percentage difference among the four groups,male to female ratio differences,age differences were not statistically significant (P ＞ 0.05).The FEV1％ pred,FEV1/ FVC,DLCO and DLCO/VA of the mild,moderate,severe and very severe of COPD patients were significantly lower than the control group (P ＜0.05),except the FEV1 ％pred of mild of COPD (P ＞ 0.05).The FEV1％pred of mild,moderate,severe and very severe of COPD decreased with the severity of COPD,coparation between each two groups were statistically significant (P ＜0.05).There is a good correlation between each lung function index,such as FEV1,FEV1/FVC,DLCO and DLCO/VA of COPD patients(P ＜0.05).Conclusions The FEV1,FEV1/FVC,DLCO,DLCO/VA of patients with COPD were lower than normal healthy people,their pulmonary ventilation function and pulmonary diffusion function had a good correlation,suggesting that lung function testing in the diagnosis of COPD had a very important clinical significance,and should be actively promoted.
Key words:
Chronic obstructive pulmonary disease; Pulmonary function testing
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Clinical Significance
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To compare high-resolution computed tomography (HRCT) of lungs with pulmonary function in smokers diagnosed with emphysema.The authors retrospectively reviewed 17 patients with a history of smoking and dyspnea, who underwent HRCT of the lungs and pulmonary function testing. HRCT scores were determined and compared to pulmonary function (FEV1, FEV1/FVC, and DLCO).The HRCT of all 17 patients (17/17; 100%) were typical of centrilobular emphysema; with a mean score of 12.88+/-9.18 (range, 4 to 34). Decreased FEV1 (<80% predicted) was found in 8 patients (47%), decreased FEV1/FVC (<70% predicted) in 13 patients (76%) and decreased DLCO (<80% predicted) in 3 patients (18%). The severity of emphysema revealed by HRCT was inversely correlated with the pulmonary function test: DLCO (r=-0.842, p=0.000) and FEV1 (r=-0.597, p= 0.011), but not FEV1/FVC (r=-0.400, p=0.112).HRCT allows detection of emphysema in symptomatic smokers even when pulmonary function appears to be normal. The greater the involvement of emphysema revealed by the HRCT, the poorer the pulmonary function. The authors, therefore, conclude that HRCT is the most sensitive modality for diagnosing early emphysema in smokers with dyspnea.
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High-resolution computed tomography
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Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) increases as lung volume increases above functional residual capacity (FRC). However, the physiological mechanism responsible for this increase remains controversial. This volume dependence of diffusing capacity could reflect changing regional distribution of inspired air as lung volume increases rather than a change in capillary blood volume or surface area for gas exchange. We measured DLCO during breath holding and during rebreathing with a technique employed to mix respired gases throughout the lung thereby minimizing regional distribution differences. Measurements were made 1,500 ml above FRC and near total lung capacity (TLC). Breath holding DLCO was 18% higher near TLC than at 1,500 ml above FRC (P less than 0.05). Rebreathing DLCO was 16% higher near TCL than at 1,500 ml above FRC (P less than 0.01). Equality of results by the two techniques indicates that changes in DLCO with lung volume are not a consequence of the changing distribution of inspired air. Our results are compatible with the hypothesis that effective surface area of the lung increases as lung volume expands.
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Residual volume
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Scleroderma is a systemic disease characterized by a severe inflammatory process with exuberant fibrosis. The pulmonary involvement (interstitial disease and/or pulmonary hypertension) is one of the first causes of mortality and morbidity.
Aim: To describe the functional involvement of the pulmonary disease in scleroderma.
Subjects and methods: Scleroderma patients with pulmonary involvement who performed pulmonary function tests (spirometry, diffusion capacity DLco, pulmonary volumes), walking tests, chest X-ray and echocardiography in 2012.
Results: 24 patients were studied, mean age 52 years, 23 women; 9 had limited cutaneous scleroderma, 12 had interstitial radiologic involvement; 16 patients had exertional dyspnoea and 5 of them exercise desaturation.
Five patients had normal pulmonary function testing. Although the mean values were normal for volumes and flows (FVC 88%, FEV1 85%, TLC 84% of the predicted values), 8 patients had restriction. Mean DLco was 68.7% (range 44–101%); decrease of DLco was found in 19 patients (79%); in 11 of them this was the only resting functional abnormality. Among patients with diffusion capacity impairment, only 14 had exertional dyspnoea and only 9 had pulmonary radiologic abnormalities.
Echocardiography was performed in 15 patients and 2 of them had pulmonary hypertension with normal pulmonary volumes and impaired diffusion capacity.
Conclusion: Complex pulmonary function tests including DLco are necessary for scleroderma patients with pulmonary involvement. The DLco is abnormal in the majority of cases, even without exertional dyspnoea or restriction. The echocardiographic evaluation is useful even in patients with mild decrease in DLco, due to the worse prognosis of pulmonary hypertension.
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Scleroderma (fungus)
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Dear Editor, Diffusion capacity of the lungs for carbon monoxide (DLCO), in combination with spirometry and lung volumes, is indicated to evaluate the parenchymal and non-parenchymal lung diseases. The preoperative DLCO is not routinely measured in patients in most cardiac surgery units. DLCO is used to assess the severity of obstructive and restrictive lung diseases, pulmonary vascular disease, and preoperative risk. The patients surviving coronavirus disease-2019 (COVID-19) are frequently reported to have pulmonary sequelae.[1] We recently encountered five patients admitted for cardiac surgery, who had contracted COVID-19 about 6–8 months ago. Preoperative assessment of the pulmonary function included chest X-ray, high-resolution computed tomography of the chest, arterial blood gas analysis at room air, and spirometry with DLCO measurement. The DLCO was measured by SPIRO AIR® volumetric PFT (pulmonary function test) System (Medisoft, Sorinnes, Belgium) using a single-breath technique. The patients' details and PFT values are shown in Table 1. There was severe impairment of DLCO and alveolar volume (Va) values (37% and 45% of predicted, respectively) in patient number one. The patient was referred for pulmonary rehabilitation and optimization of medical therapy, and was asked for a follow-up at 3 months. The remaining four patients with normal DLCO values underwent cardiac surgery uneventfully.Table 1: Patient Characteristics and Pulmonary Function Test ValuesRecent studies have shown that the lung is the most commonly affected organ by COVID-19.[1] In the initial reports from Wuhan, China, up to one-third of patients with COVID-19 developed severe pneumonia and acute respiratory distress syndrome.[2] The exact mechanism of lung dysfunction in recovered COVID-19 patients remains unknown. Endothelial injury and alveolar-capillary micro-thrombosis have been described as underlying mechanisms of pulmonary vascular disease in these patients. Due to the thickening of the alveolar-capillary membrane, there is reduction in both DLCO and Kco (transfer coefficient) in patients with interstitial lung disease and pulmonary fibrosis.[3] An isolated reduction in DLCO suggests loss of the pulmonary capillary bed from early parenchymal lung disease. In contrast to the spirometric values, DLCO is less affected by the patient's effort. Unpublished data from a recent study by Qin et al.[4] have shown that 44 (54%) of 81 patients had abnormal DLCO (<80% predicted) after 3 months of COVID-19. They also found that the patients with impaired DLCO had a higher percentage of pulmonary interstitial damage. In rehabilitating patients of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), impairment of DLCO was the most commonly seen abnormality followed by a restrictive ventilatory defect. A recent prospective, multicenter study has shown that DLCO % predicted at 4 months after COVID-19 was the most important, independent correlate of a more severe initial disease.[5] In conclusion, our case series reveals that COVID-19 survivors presenting for cardiac surgery can have impaired DLCO. Long-term studies are needed to address whether the assessment of DLCO, in addition to spirometry, should be considered in routine clinical follow-up of COVID-19 survivors. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
2019-20 coronavirus outbreak
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A study was made on the effects of relevant factors on pulmonary diffusion function and applicability of diffusion measurements in space medicine. In this experiment, diffusion measurements were made using single breath method in 120 healthy subjects and 76 patients with lung diseases. A comparative analysis was also made. The results showed that DLco and Kco in healthy subjects decreased with age. While DLco was found to be higher in male than female, positively correlated with body height, and increased with increase of VC and TLC. Kco was not affected by body height, sex or lung volume, but increased with increased percentage of FEV1 and decreased with increased percentage of RV. Although the effects of pulmonary capacity and ventilation on DLco and Kco are different, their percentages in the predicted values are similar. It showed that their changes in healthy subjects are synchronous. Both of the two parameters decreased in various pulmonary diseases. However, Kco had a sensitive response in chronic obstructive pulmonary diseases, which may be used as an index for early diagnosis of pulmonary emphysema. DLco decreased remarkably in restructive pulmonary diseases. It indicates that the two indexes of diffusion capacity respond differently to different pulmonary diseases. It may be helpful when these two parameters of pulmonary diffusion are used in combination in determining impairment in diffusion capacity for early diagnosis of pulmonary diseases.
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Pulmonary Diffusing Capacity
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The pulmonary function test (PFT) has been widely used in sarcoidosis. It may vary due to the severity, extent, and the presence of complications of the disease. Although the PFT of most sarcoidosis patients is normal, there are still 10–30% of cases who may experience a decrease in the PFT, with a progressive involvement of lungs. Restrictive ventilatory impairment due to parenchymal involvement has been commonly reported, and an obstructive pattern can also be present related to airway involvement. The PFT may influence treatment decisions. A diffusing capacity for carbon monoxide (DLCO) < 60% as well as a forced vital capacity (FVC) < 70% portends clinically significant pulmonary sarcoidosis pathology and warrants treatment. During follow-up, a 5% decline in FVC from baseline or a 10% decline in DLCO has been considered significant and reflects the disease progression. FVC has been recommended as the favored objective endpoint for monitoring the response to therapy, and an improvement in predicted FVC percentage of more than 5% is considered effective.
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Objective To investigate the effects of whole-body gamma-knife hypofractionated radiotherapy on pulmonary function in elderly non-small cell lung cancer(NSCLC) patients.Methods Forty-five patients with NSCLC were treated with whole-body gamma-knife hypofractionated radiotherapy.Prescribed radiation doses were 40~52Gy/8-12F(median dose was 48 Gy).Pulmonary function tests(PFTs) were performed before radiotherapy and at 1-,3-,6-months after radiotherapy(RT) respectively.Tests parameters included forced vital capacity(FVC),forced expiratory volume in one second(FEV1),and diffusing capacity of lung for carbon monoxide(DLCO).PFTs were expressed as a percentage of normal values.Results The overall response rate was 93.3%(42/45).The overall 1-year survival rate was 82.2%(37/45).At 1 month after RT,a significant increase was observed for the FEV1%(P0.05),but no obviously change was seen in the DLCO%.A significant decrease was in pulmonary function was observed at 3 months after RT(P0.05).The pulmonary function decreased further at 6 months after RT(P0.05).Conclusion Whole-body gamma-knife hypofractionated radiotherapy is effective for elderly non-small cell lung cancer patients.At the same time,it is harmful for pulmonary function.
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Vital capacity
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Pulmonary Diffusing Capacity
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