Bronchoalveolar pH and inflammatory biomarkers in newly diagnosed IPF and GERD patients: A case-control study

Abstract

BackgroundSeveral studies have suggested that idiopathic pulmonary fibrosis (IPF) may be related to repeated aspiration of gastric contents over long periods of time. We aimed to investigate differences between pH measured directly in the lung, and biomarkers of acute inflammation in patients with newly diagnosed IPF and in patients with newly diagnosed GERD.Material/MethodsAll subjects (N=61) underwent collection of medical history, physical examination, pulmonary function testing, bronchoscopy, endoscopy, arterial blood gas analyses, and biochemical testing.ResultsPreviously diagnosed GERD was found in 56.7%, typical symptoms of reflux in 80%, and Helicobacter pylori in gastric biopsy specimens in 76.6% of the cases. pH in peripheral branches of bronchi in the cases was 5.32±0.44 and was 6.27±0.31 (p<0.001) in the control group. The average values of LDH, ALP, and CRP in bronchoalveolar aspirate and in serum, as well as TNF-α in bronchoalveolar aspirate, were significantly higher in IPF patients.ConclusionsThe more acidic environment in the bronchoalveolar aspirate of the IPF subjects could contribute to the development or progression of IPF, possibly via changes in local metabolism or by damaging local cells and tissue. However, further studies with larger numbers of patients are required to clarify the role of gastric fluid aspiration in IPF pathogenesis. Our preliminary work has identified inflammatory biomarkers LDH, ALP, and TNF-α as potentially important in the pathologic processes in IPF. Further research is needed to determine their importance in clinical intervention and patient care.

Anti-TNFα therapy in inflammatory lung diseases

“…It is clinically characterized by a progressive decline in pulmonary function (Raghu et al, 2008). Increased levels of TNFα have been observed experimentally in the lungs of animals with pulmonary fibrosis and patients with IPF (Altintas et al, 2016; Lopez-de la Mora et al, 2015; Losa Garcia et al, 1999; Lozo Vukovac et al, 2014; Pan et al, 1996; Riha et al, 2004; Schupp et al, 2015; Vaillant et al, 1996; Zhang et al, 1993; Ziegenhagen et al, 1998). Lung tissue and alveolar macrophages isolated from patients with IPF release increased amounts of TNFα and sTNF receptors compared to healthy subjects (Cu et al, 2009; Piguet et al, 1993; Zhang et al, 1993).…”

Gastroesophageal Reflux Disease in Idiopathic Pulmonary Fibrosis: Uncertainties and Controversies

“…1) [40]. Direct evidence of microaspiration may include significantly lower pH and elevated pepsin and bile acid levels in the airway or in the BALF of lungs with IPF, which indicate acidic or nonacidic reflux (duodenal gastroesophageal reflux) [9, 10, 41, 42]. As a consequence of the injury, lactate dehydrogenase level in the bronchoalveolar aspirate is higher in patients with IPF and GERD than in healthy controls [43].…”

“…In vitro studies have revealed that bile acids, pepsin, and Hp VacA endotoxin may induce cytotoxic and inflammatory responses or epithelial-mesenchymal transition in lung epithelial cells or fibroproliferative responses in lung fibroblasts [48-50]. Controversially, however, Hp appears to be insignificantly present in the lungs of patients with IPF, as demonstrated by the analysis of DNA, histopathology of lung biopsies, and serological detection of Hp antibody [9, 38, 51]. The potential cellular and molecular mechanisms involving microaspiration in IPF are outlined in Figure 2.…”

“…Moreover, HMII (24-h multichannel intraluminal impedance) allows the measurement of bolus reflux, which provides more accurate identification of both acidic and weak acidic reflux [39]. Microaspiration may be indirectly suggested by the presence of GER [40], decreased bronchial mucosal pH [9], altered biomarker levels (e.g., pepsin, bile acids, lactate dehydrogenase, and C-reactive protein) [9, 10] or the detection of lipid-laden [55] or chlorophyllin-stained macrophages [56] in BALF, spectra of exhaled breath condensate [51, 57], induced sputum biomarkers, or atypical lung pathology [36]. A clinical trial (NCT trial No.…”

“…The current hypothesis is that gastric contents are microaspirated, which is facilitated by weakened lower esophageal sphincter (LES), to the pharyngeal region and subsequently aspirated into the lower respiratory tract. Some previous studies have supported this hypothesis by reporting the detection of gastric contents (acids and pepsin) in the bronchoalveolar lavage fluid (BALF) of patients with IPF [9, 10]; such microaspiration may stimulate the fibroproliferative responses of the lung at molecular and cellular levels [11, 12]. Furthermore, some studies found that both antacid drugs and antireflux surgery were potentially beneficial to patients with IPF [1, 2, 13], although some other studies do not agree with this claim [14, 15].…”