Two cases of chronic obstructive pulmonary disease evaluated by dynamic-ventilatory digital radiography for pulmonary function and assessment of treatment efficacy

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.


Introduction
Spirometry is a crucial test implemented in the diagnosis and monitoring of chronic obstructive pulmonary disease (COPD). However, the production of aerosols could contribute to the transmission of severe acute respiratory syndrome coronavirus 2 during the coronavirus disease 2019 (COVID-19) pandemic [1]. Recent studies have reported the utility of dynamic digital radiography (DR) performed by a flat panel detector (FDP) device [2]. Dynamic-ventilatory DR provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography (CT). These images from dynamic-ventilatory DR allow efficient examination of Abbreviations: COPD, chronic obstructive pulmonary disease; DR, digital radiography.
such respiratory kinetic parameters corresponding to the change in the area of the lung, diaphragmatic motion, and change in tracheal diameter [2e5]. Here, we report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and its treatment efficacy. This study aims to analyze the potential of dynamic DR for evaluating COPD therapy.

Dynamic-ventilatory digital radiography
Dynamic-ventilatory DR was performed as previously reported [4]. Sequential chest radiography images of the patient breathing slowly to maximum inspiration and maximum expiration were captured at 15 frames per second using a dynamic flat-panel imaging system (Test Model; Konica Minolta, Inc., Tokyo, Japan The lung areas at the points of maximum inspiration (lung area_in) and maximum expiration (lung area_ex) were measured as previously described [4]. The ratio of change in the area of the lung during a respiratory cycle (ratio of lung area change) was calculated as follows: ratio of lung area change ¼ (lung area_ex e lung area_in)/lung area_in. The change in extent of the movement of bilateral diaphragm during a respiratory cycle (diaphragm motion) was also measured as previously described [3].

Case 2
A 76-year-old man, who was scheduled to undergo surgery for lung cancer, was referred to our department after being diagnosed with an obstructive disorder based on spirometry.
The patient was a current smoker, having smoked 40 cigarettes per day for 46 years. He also had intermittent asthma The table shows treatment course in Case 1 and Case 2 on spirometry, lung volumes using multi-breath helium dilution method, forced oscillation technique and total CAT score. COPD was diagnosed in Case 1, who was reassessed after 3 months of treatment with indacaterol/glycopyrronium. Asthma/COPD overlap syndrome was diagnosed in Case 2, who was reassessed after 2 weeks of treatment with the combination of fluticasone/ formoterol and tiotropium.
r e s p i r a t o r y i n v e s t i g a t i o n 5 9 ( 2 0 2 1 ) 8 7 1 e8 7 5 and allergic rhinitis since about 40 years of age, although he did not receive regular treatment for asthma. His CAT score was 4. Pulmonary function testing revealed an obstructive pattern prior to bronchodilator administration as follows: VC,  Fig. 1 e The ratio of the change in lung area over a single respiratory cycle in Case 1 and Case 2. Sequential chest radiography images of the patient breathing slowly to maximum inspiration and maximum expiration were captured at 15 frames per second using a dynamic flat-panel imaging system (Test Model; Konica Minolta, Inc., Tokyo, Japan). The ratio of the change in lung area over a single respiratory cycle (maximum inspiration to maximum expiration) was calculated as follows: ratio of the change in lung area ¼ (lung area at maximum expiration e lung area at maximum inspiration)/lung area at maximum inspiration. In Case 1, the lung area ratio changed from ¡0.22 to ¡0.27 with treatment (Fig. 1a). In Case 2, the lung area ratio changed from ¡0.30 to ¡0.34 with treatment (Fig. 1b).
results of spirometry following bronchodilator administration were as follows: VC, 3.11 L (%VC, 97.8%); FVC, 3.11 L (%FVC, 97.8%); FEV 1 1.60 L (%FEV 1 , 70.8%); FEV 1 /FVC 51.4%. The exhaled nitric oxide level was 22 ppb. His peripheral blood eosinophil count was 168/mL, and his total IgE level was 1449 IU/mL. Asthma/COPD overlap syndrome was diagnosed based on the data, and the patient started combination therapy consisting of fluticasone/formoterol and tiotropium. Two weeks following the initiation of combination therapy, the patient's CAT score and pulmonary function showed significant improvement ( Table 1). The ratio of the change in lung area as well as bilateral diaphragm motion increased following the treatment (Figs. 1b and 2

Discussion
We evaluated the therapeutic effects of COPD treatments for two patients using dynamic DR in addition with spirometry, measurement of lung volumes, forced oscillation technique, and the determination of CAT scores. The ratio of change in the lung area and the bilateral diaphragm motion during a respiratory cycle increased following the treatment in both cases. These results reflect improvements in pulmonary hyperinflation following treatment with bronchodilators or inhaled corticosteroid. Recent studies have shown that the parameters obtained from dynamic DR are useful measures that reflect the pulmonary function of patients with COPD [3e5]. To the best of our knowledge, this is the first report on the efficacy of dynamic DR in the verification of therapy for COPD.
These findings are consistent with previous findings that the ratio of the change in lung area during a respiratory cycle reflect the severity of airflow limitation [3,4]. On the other hand, the diaphragm motion during tidal breathing have been reported to be larger in COPD patients than in healthy volunteers [6]. Discrepancy of the diaphragmatic movement due to breathing maneuvers is a future issue for elucidation of the pathophysiology of COPD.
The evaluation of pulmonary function by dynamic DR has numerous advantages over other modalities. For instance, dynamic DR can be performed with a patient either in a standing or sitting position, both of which reflect physiologically relevant routine activities. Dynamic DR can be conducted as a supplemental examination to conventional chest radiography. The radiation dose of dynamic DR is lower than that of conventional X-ray fluoroscopy and CT [7]. Dynamic DR, unlike spirometry, does not require forced expiration or techniques that depend on the skill of the operator or on the cooperation of the patient being evaluated. Since dynamic DR is a noninvasive evaluation and is easy to perform, even patients at a critical stage can be repeatedly tested. Additionally, the sequential chest X-ray images provided by dynamic DR [4] during respiration may facilitate the understanding of chest respiratory motions for both the operator and the patient. Therefore, this imaging modality contributes to a patient's understanding of the disease and thereby increase patient adherence to treatment.
COVID-19 pandemic has led to numerous complications while performing spirometry. The Japanese Respiratory Society recommends using flowchart entitled "Working diagnosis and initial management of COPD during the COVID-19 pandemic" for the diagnosis of COPD in cases where spirometry cannot be performed [8]. In the flowchart, the evaluation of treatment efficacy relies exclusively on the changes of CAT score. However, dynamic-ventilatory DR system could be used by physicians to confirm treatment efficacy. However, the limitations of the study should be considered. First, we cannot show the minimal clinical important difference values obtained from the dynamic-ventilatory DR yet. Second, asynchrony of chest wall motion as well as vertebral deformity may affect parameters such as diaphragmatic motion, and lung area change rate. These 2 cases did not exhibit asynchrony of chest wall motion and vertebral deformity (Supplemental file 1a, 2a). Therefore, we need to consider if abnormal findings on chest X-ray may affect the parameters achieved using dynamic-ventilatory DR. Therefore, further investigations are required to address these issues.
In conclusion, dynamic-ventilatory DR is a promising tool for monitoring the pulmonary function of patients with COPD.

Conflict of interest
This study was supported by Konica Minolta, Inc. (Tokyo, Japan). NOhkura received honoraria for writing promotional material for a device by Konica Minolta, Inc. RT received honoraria for writing promotional material for a device by Konica Minolta, Inc. NOhkura has been reimbursed by Konica Minolta Inc. for attending several conferences. RT has been reimbursed by Konica Minolta Inc. for attending several conferences. KK has been reimbursed by Konica Minolta Inc. for attending several conferences. KK received a research grant from Konica Minolta, Inc.