In this study, we demonstrated that MRI with DWI identified lung inflammatory lesions in patients with PAD. Moreover, we confirmed our previous data on the non-inferiority of MRI
vs HRCT scan [
29]. HRCT is the gold standard in the lung structural damage evaluation for its excellent spatial resolution, fast acquisition times and wide availability [
30]. However, HRCT poses concerns regarding the radiation dose, mostly in CVID patients, a population with a suggested increased radio sensitivity undergoing a long life follow-up [
14‐
19]. Therefore, for these subjects, radiation-free imaging would be desirable for both follow-up and therapy monitoring. Nowadays, several strategies have been developed to overcome the inherent technical limitations of lung MRI and this imaging modality is becoming a promising tool in different diseases, including primary immune deficiencies such as ataxia-telangiectasia [
31]. The implementation of DWI sequences enabled the acquisition of valuable information regarding the microstructure of tissues, allowing the identification of several pathological processes, including active inflammation [
21‐
24,
32,
33]. In a previous cross-sectional study, we have demonstrated that MRI with BLADE sequences was a reliable technique in the detection of bronchial and parenchymal alterations and provided information overlapping HRCT [
20]. We confirmed our previous data and we showed high levels of concordance between HRCT and MRI in scoring bronchiectasis severity, extent of bronchiectasis and mucus plugging. However, HRCT had a higher capacity to identify the involvement of bronchial generation up to the fifth and distal. We showed here that the inclusion of DWI sequences might provide valuable records to detect the presence of areas of active inflammation. Other radiological procedures, such as Positron Emission Tomography-CT, have been proposed for localization and quantification of active inflammation in the lung [
34,
35]. However, their use is restricted by high ionizing radiation exposure, cost and limited availability.
For DWI image analysis, we used an adapted Bhalla scoring system taking into account all the alterations showing equal or higher signal intensity compared to the spinal cord at the highest b value. This technique, already adopted in previous experiences [
36], did not imply a quantitative analysis derived from Apparent Diffusion Coefficient maps, it is hardly adaptable to lung imaging for its low proton density, B0 inhomogeneity, and physiologic motion. Moreover, the presence of susceptibility artefacts would lead to difficulty and poor reproducibility in selecting a consistent region of interest.
In this cohort, MRI protocol was able to identify lung alterations occurring in PAD patients; our results showed that a semi-quantitative assessment with a scoring system was feasible and matched well with the total mean HRCT scores and PFTs of the same patients. In our cohort, the MRI evaluation showed that bronchial abnormalities were the prevalent finding in PAD patients. These abnormalities might be considered as signs of chronic, active inflammation and/or infections. [
1‐
5]. Thus, as previously suggested [
3] aside from Ig replacement, a strategy to reduce the chronic mucosal damage should be defined. Chronic antibiotics treatment was suggested but its efficacy is still matter of discussion [
37]; now we are conducting a large double blind study about prophylaxis with azithromycin in PAD in order to prove a possible benefit in reducing respiratory exacerbations as shown in patients with non-cystic fibrosis bronchiectasis [
38]. Even if Ig therapy could not reduce the progression of lung diseases and damage, we documented an improvement of parenchymal and bronchial scores and of PFTs in newly diagnosed PAD patients after the beginning of Ig replacement therapy. We found a significant relationship between the extent of MRI bronchial abnormalities score and PFTs. Based on these findings, it appears that PFTs alterations were strictly connected to a bronchial damage. However, MRI parenchymal scores did not correlate with PTFs, including D
LCO. This was not surprising since none of the patients enrolled had bullae, only few patients had a mild emphysema and none had clinical signs of acute pulmonary infection at the time of the study. Moreover, MRI was able to identify active bronchial abnormalities in a group of patients with normal PFTs. The interpretation of DWI findings may represent a useful tool in addition to the conventional morphological analysis, mostly in subjects with advanced disease. In our evaluation, all DWI hotspots corresponded to morphological alterations, but not vice versa: lung pathological findings showed different DWI patterns or no DWI signal at all. It can be postulated that the mismatch between DWI and morphological data correlates with cellular and extra-cellular space modifications (density/composition/water content) induced by active inflammation: these phenomena may affect DWI even before macroscopic alterations can be detected on conventional imaging. DWI parenchymal restricted areas were mainly detected in patients with severe total and parenchymal scores and with more severe alterations of PFTs. They were associated with abnormalities described in patients with the inflammatory CVID phenotypes: systemic granulomatous disease, systemic lymphadenopathy, expansion of CD21
low B cells [
39]. For these reasons, DWI might represent a marker of disease activity and it could be used during follow-up of PAD patients in order to distinguish
foci of active inflammation/sub-clinically progressive lung disease from chronic pathological manifestations [
8‐
11]. The presence of inflammation represents an important pathological process underlying many lung morphological alterations in PAD patients and, in the clinical practice, it is important to determine the activity of disease to guide interventions. DWI sequences, with the possible identification of active inflammation, may allow an early discrimination of patients with infective/inflammatory or non-infective/inflammatory disease. Inflammatory lung diseases in CVID have been reported to be associated with lung disease progression and increased mortality [
11,
40,
41], but the timing when starting an immunosuppressive treatment is still open [
42‐
44]. Moreover, since MRI is a radiation-free technique, it can be repeatedly used in follow-up monitoring of treatment response, differentiating between active and fibrotic lesions.