The complex relationship between GERD and respiratory disorders remains controversial due to a lack of evidence of clear, conclusive causality, although recent studies support this relationship [12]. There is an increasing body of evidence supporting the role of GERD in facilitating lung damage and, similarly, in a bi-directional fashion, the role of pulmonary disorders in the development of GERD [11, 13,14,15]. Furthermore, the Pulmonary Fibrosis Consensus Group of the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax extensively debate the role of GERD in the development and progression of idiopathic pulmonary fibrosis (IPF) in recently updated clinical practice guidelines [16]; on the one hand, the development of IPF is multifactorial, but on the other hand, the role of GERD as either a trigger or contributor to other underlying causes cannot be ignored.

Further, the deliberated chronic use of acid suppression therapy may accentuate the consequences of repetitive silent micro-aspiration. As documented in our study, almost all GERD patients (97.2%) received acid suppression therapy before mechanical control (i.e., ARS); however, although these medications increase the pH of refluxed material and control the most frequent symptoms, their use does not prevent aspiration events. Of note, nearly all studies looking for a treatment for GERD in IPF patients have incorporated and evaluated the use of acid suppression therapy, and their results are conflicting [17]. While some favor the use of proton pump inhibitors (providing stabilization of functional lung capacity and reduction of disease exacerbations), others report that their use in patients with IPF do not provide additional benefits and even leads to unexpected complications (e.g., increased risk of respiratory infections [17].

On the other hand, case series and studies have reported that mechanical control of reflux (i.e., ARS) is safe and improves pulmonary function; however, the inference is very limited due to the nature of this observation [18,19,20]. In the randomized controlled trial WRAP-IPF by Raghu et al. [21], the authors explored the protective role of ARS in patients with IPF. They found a trend toward fewer respiratory-related complications and lower mortality among patients who underwent ARS compared to those who were medically treated. Unfortunately, the study was limited not only by the sample size but also, more importantly, by the inclusion of only patients with late-stage IPF [21].

In our opinion, the resulting quagmire is caused by the absence of early non-invasive and reliable biomarkers of GERD-related pulmonary disease, which often goes clinically unsuspected and is managed symptomatically until late stages. A reliable non-invasive marker of pulmonary parenchymal injury would greatly improve diagnosis and hence treatment in the early stages of the disease. If such a marker is associated with certain phenotypes of GERD, developing strategies for the definitive treatment of GERD will improve patient management and potentially lead to the prevention of continued lung injury.

The expected prevalence of seropositivity of antibodies against normally sequestered SAgs Col-V and Kα1T among healthy individuals is 2.9–5% [22, 23]. In our study, we identified a high prevalence of seropositivity among patients undergoing ARS (i.e., up to 69.8%), meaning that these patients may have unsuspected underlying parenchymal damage. Of note, in the present series, patients who presented with volume reflux (i.e., those who usually display a variety of typical GERD symptoms such as regurgitation and often atypical manifestations like cough, asthma, or dental erosions [24]) had a higher seroprevalence of abnormally elevated concentrations of SAbs than individuals who underwent ARS due to obstructive symptomatology (i.e., dysphagia) or complications resulting from a large HH (i.e., chronic anemia). Although inconclusive, this finding lends further evidence to the theory that aspiration of gastric contents may trigger the mechanism that induces the expression of SAbs.

There may be some caveats in using these humoral factors as a screening tool for lung damage among GERD patients. Indeed, the immunogenic profile of each SAg and the de novo expression of their corresponding SAb may differ. For example, factors including respiratory viral infections, smoking, and preexisting lung disorders may facilitate the initiation of this immune response, hence, the causes may be multifactorial [7]. In addition, a few studies have reported the abnormal expression of these SAbs in the context of other conditions, including breast cancer, small cell lung carcinoma, and transplant-related cardiomyopathy [25, 26].

This study has multiple limitations. There was a relatively small sample size, which limited further statistical analysis, and the single-center design may limit the generalizability of the findings. Also, our study lacks an objective respiratory evaluation (i.e., functional respiratory test or the use of validated tools) that may be relevant to establishing an association between SAb concentrations and clinical status or presentation. Furthermore, not all of the patients had complete preoperative testing, which precluded exploring correlations of SAb concentrations with specific pH metrics. In the future, it would be desirable to also include impedance testing to assess the correlation of SAbs with non-acidic reflux events as well as other potential diagnostic modalities (e.g., histological assessment, computed tomography, etc.) to document objective evidence of established lung damage. The use of other biomarkers in future research may help to determine whether aspiration is occurring (e.g., pepsin or pepsinogen A4 in bronchoalveolar lavage fluid or saliva). Finally, confounders such as autoimmune disorders or environmental factors were not assessed, and the study’s cross-sectional analysis and descriptive nature preclude causal inference.