After its introduction in 1956 [1], whole-body plethysmography has been regarded as gold standard for measuring static lung volumes including residual volume (RV), functional residual capacity (FRC) and total lung capacity (TLC). Methods based upon multiple-breath gas dilution or washout techniques depend on communicating gas and thus only measure a subject’s ventilated lung volumes. In contrast, plethysmography includes also trapped air so it is applicable for patients with lung diseases characterized by air trapping such as chronic obstructive pulmonary disease (COPD) [2]. Performing the necessary respiratory maneuvers correctly requires meticulous coaching and multiple attempts [3]. This can be especially demanding for patients with severely impaired lung function and might not be suitable for patients (e.g. children) who find it challenging to follow instruction. In addition, the intermittent closure of air flow and compact dimensions of the body box can induce panic attacks in patients suffering from claustrophobia.

CT lung volumetrics is promising as an alternative tool for assessing pulmonary function and volumes. Furthermore, software can both quantify degree of emphysema and segment the lung into pulmonary lobes, which is helpful when selecting lobes as target for lung volume reduction therapy.

A technician or voice recording usually instructs the patient to fully inhale or exhale and hold still as the CT scan is performed. Patient cooperation and scan timing is among the challenges faced and can be managed by spirometry-gating and other solutions.

The aim of this systematic review is to assess the agreement between static lung volumes measured by quantitative CT volumetrics and body plethysmography and explore the attempts being made to optimize alignment. It is hypothesized that inspiratory CT-based volumes underestimate TLC and expiratory CT-based volumes overestimate RV whereas spirometry gating reduces the level of disagreement.

The findings of the present review suggest that discrepancy between plethysmography- and CT-derived lung volumes is a universal phenomenon. Specifically, quantitative CT routinely underestimates TLC and overestimates RV in comparison to body plethysmography. Utilizing a spirometer to gate CT acquisition reduces disagreement noticeably though it does not eliminate it entirely.

TLC can be defined as the total gas volume in the lung after a full inspiratory maneuver [3]. It has been challenging to determine whether gas in the conductive airways is included in this definition. Even though it might seem trivial, this appears to be an import factor to consider. Body plethysmography incorporates volumes in the oropharynx, trachea, and anatomic dead space in the main conducting airways [10]. Some types of CT segmentation software include gas volumes in the tracheobronchial tree, others do not. For instance, the post-processing software used in Shen M et al.’s study excluded these volumes [10]. In contrast, Tantucci C et al. included anatomic dead space of 150 mL in their CT-TLC calculations [15]. Compressed gas in the upper gastrointestinal tract might also further increase FRC, which forms the basis for TLC and RV calculations [3].

Another important factor to note is the difference in posture (supine in CT vs. upright position in body plethysmography). By comparing conventional supine CT with upright CT in a specialized CT scanner, a study demonstrated that CT-based inspiratory and expiratory volumes were significantly smaller in the supine position than in the standing and sitting position in healthy subjects [27]. This is largely due to abdominal content pressing up against the diaphragm in the supine position, which has been shown by other studies to reduce vital capacity by less than 10% in normal subjects [17]. This is consistent with the results from the present review showing that CT-TLC is smaller than p-TLC.

However, the above studies contradict the present findings of a generally negative ΔRV (Table 3). This may be due to various CT software packages include lung tissue and blood vessels in their TLC volumetrics, which proportionally makes up more of the total lung volume at full expiration. ΔRV was largely based on data from COPD patients, a disease characterized by hyperinflation and an impaired ability to fully expire. Perhaps, the supine position exacerbates an already present muscle weakness, such as in the accessory expiratory muscles.

Tantucci C et al. calibrated CT and plethysmography TLC results by adding or subtracting the difference between vital capacity obtained in the seated and supine position, respectively, and presented excellent correlations [15] (Table 2).

Body plethysmography measures pressure changes at the mouth opening based on the assumption that these reflect pressure changes in the alveoli during shutter valve occlusion. In the presence of airway obstruction, however, this assumption might fail. O’Donnell CR et al. find that a worsening in airway obstruction leads to increasing overestimation of TLC, which might be due to an incomplete transmission of alveolar pressure changes to the mouth [28]. This may be part of the reason for ΔTLC being slightly larger in studies with data from obstructive patients.

Plethysmography is a very standardized method of determining lung volumes with universally applied guidelines by the American Thoracic Society and the European Respiratory Society [3]. A skilled technician instructs the patient to perform a sequence of respiratory maneuvers, and multiple attempts are made to obtain repeatability of the volume results to correct for variability in patient effort and cooperation, which can be monitored simultaneously.

Due to radiation concerns, CT acquisition is rarely repeated, and thus such unpredictable errors cannot be rectified. This becomes increasingly relevant in patients having difficulty maintaining inspiratory and expiratory breath-hold during the scan due to dyspnea. It is not possible to confirm with certainty the amount of effort patients put into following instructions. As CT accuracy depends on subject performance, being able to monitor patient effort becomes crucial in determining reliability of volume quantifications as well as certain qualitative radiological descriptions.

Bakker JT et al. showed that utilizing a spirometer can help bring CT-based volumes to a closer alignment with plethysmography measurements in patients with severe emphysema [7].

Spirometry gating is an easily applicable tool and largely tolerant to subject’s cooperation. Although studies on this are limited, the technique shows great promise in minimizing disagreements ascribable to patient effort or cooperation between patient and instructor. This would be relevant for patients already undergoing inspiratory and expiratory CT evaluation, such as candidates for lung volume reduction surgery or lung transplantation. For patients without a CT appointment, these improvements do not justify body plethysmography being replaced by spirometry-gated CT as radiation is still a concern.

Spirometers with a shutter valve are also available ensuring total control of airflow. However, Kauczor HU et al. had to discontinue spirometry gating with shutter occlusion as four out of five subjects took the device out of their mouth for both inspiratory and expiratory CT acquisition [9]. Sudden blockage of airflow may not be tolerated by all patients, in particular children, patients suffering from claustrophobia, and patients prone to anxiety, which many people with COPD experience [29].

CT machines differ in scan time ranging from one to several seconds. Many patients with severe lung disease are not capable of holding their breath for the required amount of time – regardless of spirometry gating. The studies using a spirometer scanned their patients within 6 seconds. Thus, their results may not be applicable in hospital departments with slow scanners. Other CT specifications, such as a difference in slice thickness, do not seem to have a significant impact on the results (Table A3).

The limitations of the present review need to be addressed. It was decided to narrow down the literature search, which entails a risk of missing eligible articles. In addition, this review is based on results from one single database, PubMed. It is possible that the results would be different if the search had included more databases e.g. Embase. The good congruence between both modalities may be attributed to the fact that publishers tend to exclude studies if their findings contradict current research in the area.

Another limitation may stem from individual variations in age distribution. Most studies predominantly involved middle-aged patients in their 50s and 60s. However, three studies by Chen F et al. Lacerda LS et al. and Schlesinger AE et al. included younger groups with mean ages of 42, 27 and 11 years, respectively [18–20]. As expected, the first two studies aligned well with overall findings, as they included adult participants whose body composition and size are comparable to those of middle-aged patients.

It might be anticipated that the smaller lung volume of Schlesinger AE et al.’s group, consisting of children with lung transplants aged 3 to 18 years, would result in a smaller absolute difference in total lung capacity, while percentage deviation would likely remain consistent with general outcomes of this study [18]. However, only a correlation coefficient for TLC was provided, which stood at 0.92, indicating a strong correlation as expected.

Based on the QUADAS-2 risk of bias assessment, 16 articles included domains with high risk of bias, whereas two articles demonstrated a low risk of bias. An inappropriately long time interval between plethysmography and CT leads to a high risk rating in the flow and timing domain. Four studies were unclear, as they did not provide sufficient information to assess the domains of interest. The majority of studies were retrospective and they used data originally collected for other purposes. Moreover, there is a risk of extracting patient data out of convenience rather than relevance in this type of study. For instance, Lacerda LS et al. scored a high risk of bias in the patient selection domain due to their study being based on a convenience sample of patients [19]. Yet, there seems to be no difference between retrospective and prospective studies regarding their results.

CT-based volume quantifications align well with lung volumes measured in the whole-body plethysmograph, although a clear tendency to underestimate TLC and overestimate RV in comparison to gold standard plethysmography is evident. Spirometry gating continues to be a suitable tool to reduce disagreement and can be of assistance when patients are already undergoing CT. However, research on this instrument is scarce and limitations of the present review should be considered. Standardization of CT software and further research is needed before evaluation of the static volumes of pulmonary function can be fully based on CT.